JP2004508404A - 鎮痛手法 - Google Patents
鎮痛手法 Download PDFInfo
- Publication number
- JP2004508404A JP2004508404A JP2002526380A JP2002526380A JP2004508404A JP 2004508404 A JP2004508404 A JP 2004508404A JP 2002526380 A JP2002526380 A JP 2002526380A JP 2002526380 A JP2002526380 A JP 2002526380A JP 2004508404 A JP2004508404 A JP 2004508404A
- Authority
- JP
- Japan
- Prior art keywords
- pain
- tetrodotoxin
- ttx
- administration
- sodium channel
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 54
- 230000000202 analgesic effect Effects 0.000 title description 34
- 208000002193 Pain Diseases 0.000 claims abstract description 228
- 230000036407 pain Effects 0.000 claims abstract description 185
- 108010052164 Sodium Channels Proteins 0.000 claims abstract description 41
- 102000018674 Sodium Channels Human genes 0.000 claims abstract description 41
- 150000001875 compounds Chemical class 0.000 claims abstract description 32
- 230000000903 blocking effect Effects 0.000 claims abstract description 21
- 239000000203 mixture Substances 0.000 claims abstract description 13
- 241000124008 Mammalia Species 0.000 claims abstract description 10
- 230000036592 analgesia Effects 0.000 claims abstract description 5
- 239000003937 drug carrier Substances 0.000 claims abstract description 4
- CFMYXEVWODSLAX-QOZOJKKESA-N tetrodotoxin Chemical compound O([C@@]([C@H]1O)(O)O[C@H]2[C@@]3(O)CO)[C@H]3[C@@H](O)[C@]11[C@H]2[C@@H](O)N=C(N)N1 CFMYXEVWODSLAX-QOZOJKKESA-N 0.000 claims description 318
- CFMYXEVWODSLAX-UHFFFAOYSA-N tetrodotoxin Natural products C12C(O)NC(=N)NC2(C2O)C(O)C3C(CO)(O)C1OC2(O)O3 CFMYXEVWODSLAX-UHFFFAOYSA-N 0.000 claims description 298
- 229950010357 tetrodotoxin Drugs 0.000 claims description 290
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 59
- 238000011282 treatment Methods 0.000 claims description 50
- 230000000694 effects Effects 0.000 claims description 48
- 206010028980 Neoplasm Diseases 0.000 claims description 44
- 201000011510 cancer Diseases 0.000 claims description 38
- 238000002347 injection Methods 0.000 claims description 25
- 239000007924 injection Substances 0.000 claims description 25
- 239000000126 substance Substances 0.000 claims description 19
- 230000037396 body weight Effects 0.000 claims description 12
- 230000004054 inflammatory process Effects 0.000 claims description 11
- 206010061218 Inflammation Diseases 0.000 claims description 10
- 208000004296 neuralgia Diseases 0.000 claims description 10
- 208000021722 neuropathic pain Diseases 0.000 claims description 10
- 210000004185 liver Anatomy 0.000 claims description 8
- 239000000243 solution Substances 0.000 claims description 8
- -1 tetroda aminotoxin Chemical compound 0.000 claims description 8
- 238000010255 intramuscular injection Methods 0.000 claims description 7
- 239000007927 intramuscular injection Substances 0.000 claims description 7
- 210000003205 muscle Anatomy 0.000 claims description 7
- 238000007910 systemic administration Methods 0.000 claims description 7
- 210000002784 stomach Anatomy 0.000 claims description 6
- 230000002792 vascular Effects 0.000 claims description 6
- 206010020751 Hypersensitivity Diseases 0.000 claims description 5
- 210000000988 bone and bone Anatomy 0.000 claims description 5
- 210000000481 breast Anatomy 0.000 claims description 5
- 230000007794 irritation Effects 0.000 claims description 5
- 210000004072 lung Anatomy 0.000 claims description 5
- 206010018910 Haemolysis Diseases 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- COVOMQKTVSVWBZ-CJCGOCGYSA-N deoxytetrodotoxin Chemical compound O1C(C2(O)CO)(O)OC3C(O)C1[C@@H]1CN=C(N)NC12C3O COVOMQKTVSVWBZ-CJCGOCGYSA-N 0.000 claims description 4
- 230000008588 hemolysis Effects 0.000 claims description 4
- STNXQECXKDMLJK-UHFFFAOYSA-N (4betaO)-4,9-anhydro-tetrodotoxin Natural products C12C(C3(O)CO)OC4(O)C5OC2N=C(N)NC15C(O)C3O4 STNXQECXKDMLJK-UHFFFAOYSA-N 0.000 claims description 3
- FFOVFIRMBLLEJP-UHFFFAOYSA-N 2,3,4,7-tetrahydro-1h-purine Chemical group N1CNC=C2NC=NC21 FFOVFIRMBLLEJP-UHFFFAOYSA-N 0.000 claims description 3
- PPEKGEBBBBNZKS-UHFFFAOYSA-N Neosaxitoxin Natural products N=C1N(O)C(COC(=O)N)C2N=C(N)NC22C(O)(O)CCN21 PPEKGEBBBBNZKS-UHFFFAOYSA-N 0.000 claims description 3
- MWPMJZZQPDXVJT-UHFFFAOYSA-N Tetrodonic acid Natural products N1C(N)=NC2OC(C(O)=O)C31C2C(O)C(O)(CO)C(O)C3O MWPMJZZQPDXVJT-UHFFFAOYSA-N 0.000 claims description 3
- 239000000443 aerosol Substances 0.000 claims description 3
- STNXQECXKDMLJK-NLWUVLGBSA-N anhydroepitetrodotoxin Chemical compound C12C([C@@]3(O)CO)O[C@@]4(O)[C@H]5OC2N=C(N)N[C@@]15[C@H](O)[C@@H]3O4 STNXQECXKDMLJK-NLWUVLGBSA-N 0.000 claims description 3
- 210000001072 colon Anatomy 0.000 claims description 3
- 206010013663 drug dependence Diseases 0.000 claims description 3
- 210000003238 esophagus Anatomy 0.000 claims description 3
- 230000002496 gastric effect Effects 0.000 claims description 3
- ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 3
- 238000010253 intravenous injection Methods 0.000 claims description 3
- 210000002751 lymph Anatomy 0.000 claims description 3
- SVOKHTHBCRETOQ-CNKCMGRGSA-N methoxytetrodotoxin Chemical compound OC1C(C2O)OC3(O)OC2[C@@H]2[C@@H](OC)N=C(N)NC21C3(O)CO SVOKHTHBCRETOQ-CNKCMGRGSA-N 0.000 claims description 3
- PPEKGEBBBBNZKS-HGRQIUPRSA-N neosaxitoxin Chemical compound N=C1N(O)[C@@H](COC(=O)N)[C@@H]2NC(=N)N[C@@]22C(O)(O)CCN21 PPEKGEBBBBNZKS-HGRQIUPRSA-N 0.000 claims description 3
- 210000002307 prostate Anatomy 0.000 claims description 3
- 208000011117 substance-related disease Diseases 0.000 claims description 3
- 239000000829 suppository Substances 0.000 claims description 3
- MWPMJZZQPDXVJT-JTUKEBEQSA-N tetrodonicacid Chemical compound [C@]12([C@H](C(O)=O)O[C@@H]3N=C(N1)N)[C@@H]3[C@@H](O)[C@@](O)(CO)[C@H](O)[C@@H]2O MWPMJZZQPDXVJT-JTUKEBEQSA-N 0.000 claims description 3
- 102000008186 Collagen Human genes 0.000 claims description 2
- 108010035532 Collagen Proteins 0.000 claims description 2
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 229920001436 collagen Polymers 0.000 claims description 2
- 210000004392 genitalia Anatomy 0.000 claims description 2
- 238000002513 implantation Methods 0.000 claims description 2
- 230000000302 ischemic effect Effects 0.000 claims description 2
- 230000003204 osmotic effect Effects 0.000 claims description 2
- 210000002460 smooth muscle Anatomy 0.000 claims description 2
- 238000010254 subcutaneous injection Methods 0.000 claims description 2
- 239000007929 subcutaneous injection Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 208000000453 Skin Neoplasms Diseases 0.000 claims 1
- 230000001079 digestive effect Effects 0.000 claims 1
- 230000002500 effect on skin Effects 0.000 claims 1
- 230000002427 irreversible effect Effects 0.000 claims 1
- 208000016847 malignant urinary system neoplasm Diseases 0.000 claims 1
- 239000011505 plaster Substances 0.000 claims 1
- 230000000241 respiratory effect Effects 0.000 claims 1
- 201000000849 skin cancer Diseases 0.000 claims 1
- 201000004435 urinary system cancer Diseases 0.000 claims 1
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 67
- 241000699670 Mus sp. Species 0.000 description 59
- 238000012360 testing method Methods 0.000 description 55
- 241000700159 Rattus Species 0.000 description 34
- 229960005181 morphine Drugs 0.000 description 33
- 239000013641 positive control Substances 0.000 description 30
- 239000000730 antalgic agent Substances 0.000 description 27
- 208000000094 Chronic Pain Diseases 0.000 description 24
- 241000282693 Cercopithecidae Species 0.000 description 23
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 23
- 208000024891 symptom Diseases 0.000 description 23
- 229940035676 analgesics Drugs 0.000 description 22
- 239000011780 sodium chloride Substances 0.000 description 22
- 239000003814 drug Substances 0.000 description 20
- 241001465754 Metazoa Species 0.000 description 19
- 229960000583 acetic acid Drugs 0.000 description 19
- 238000011156 evaluation Methods 0.000 description 19
- 230000034994 death Effects 0.000 description 18
- 231100000517 death Toxicity 0.000 description 18
- 229940079593 drug Drugs 0.000 description 18
- 208000005298 acute pain Diseases 0.000 description 17
- 210000005036 nerve Anatomy 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 15
- 241000699666 Mus <mouse, genus> Species 0.000 description 15
- 230000006378 damage Effects 0.000 description 15
- 230000001965 increasing effect Effects 0.000 description 15
- 230000004044 response Effects 0.000 description 14
- RPQXVSUAYFXFJA-HGRQIUPRSA-N saxitoxin Chemical compound NC(=O)OC[C@@H]1N=C(N)N2CCC(O)(O)[C@@]22N=C(N)N[C@@H]12 RPQXVSUAYFXFJA-HGRQIUPRSA-N 0.000 description 14
- RPQXVSUAYFXFJA-UHFFFAOYSA-N saxitoxin hydrate Natural products NC(=O)OCC1N=C(N)N2CCC(O)(O)C22NC(N)=NC12 RPQXVSUAYFXFJA-UHFFFAOYSA-N 0.000 description 14
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 13
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 13
- 210000003169 central nervous system Anatomy 0.000 description 13
- 238000007918 intramuscular administration Methods 0.000 description 13
- 230000001953 sensory effect Effects 0.000 description 13
- 210000003594 spinal ganglia Anatomy 0.000 description 13
- 238000001356 surgical procedure Methods 0.000 description 13
- 108091006146 Channels Proteins 0.000 description 12
- 241000283973 Oryctolagus cuniculus Species 0.000 description 12
- 229960001138 acetylsalicylic acid Drugs 0.000 description 12
- 230000003247 decreasing effect Effects 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 11
- 210000003414 extremity Anatomy 0.000 description 11
- 239000000463 material Substances 0.000 description 11
- 208000031404 Chromosome Aberrations Diseases 0.000 description 10
- 230000005856 abnormality Effects 0.000 description 10
- 230000004913 activation Effects 0.000 description 10
- 239000002504 physiological saline solution Substances 0.000 description 10
- 239000003981 vehicle Substances 0.000 description 10
- 208000005890 Neuroma Diseases 0.000 description 9
- 230000002159 abnormal effect Effects 0.000 description 9
- 230000002354 daily effect Effects 0.000 description 9
- 238000009826 distribution Methods 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 239000003195 sodium channel blocking agent Substances 0.000 description 9
- 230000000638 stimulation Effects 0.000 description 9
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 8
- 241000607142 Salmonella Species 0.000 description 8
- 230000001154 acute effect Effects 0.000 description 8
- 238000010171 animal model Methods 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- 231100000005 chromosome aberration Toxicity 0.000 description 8
- 229960004397 cyclophosphamide Drugs 0.000 description 8
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 8
- 229960003529 diazepam Drugs 0.000 description 8
- 230000003400 hallucinatory effect Effects 0.000 description 8
- 208000014674 injury Diseases 0.000 description 8
- 239000013642 negative control Substances 0.000 description 8
- 210000000929 nociceptor Anatomy 0.000 description 8
- 108091008700 nociceptors Proteins 0.000 description 8
- 229940005483 opioid analgesics Drugs 0.000 description 8
- 230000001575 pathological effect Effects 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 102100031374 Sodium channel protein type 10 subunit alpha Human genes 0.000 description 7
- 206010047700 Vomiting Diseases 0.000 description 7
- 208000027418 Wounds and injury Diseases 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 230000036541 health Effects 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 7
- 201000007270 liver cancer Diseases 0.000 description 7
- 208000014018 liver neoplasm Diseases 0.000 description 7
- 238000007920 subcutaneous administration Methods 0.000 description 7
- 208000004998 Abdominal Pain Diseases 0.000 description 6
- 206010058019 Cancer Pain Diseases 0.000 description 6
- 208000000059 Dyspnea Diseases 0.000 description 6
- 206010013975 Dyspnoeas Diseases 0.000 description 6
- 208000035154 Hyperesthesia Diseases 0.000 description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
- 230000006399 behavior Effects 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 230000002503 metabolic effect Effects 0.000 description 6
- 230000001537 neural effect Effects 0.000 description 6
- 229940121367 non-opioid analgesics Drugs 0.000 description 6
- 239000000014 opioid analgesic Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 206010064012 Central pain syndrome Diseases 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 208000004454 Hyperalgesia Diseases 0.000 description 5
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 5
- 241000700157 Rattus norvegicus Species 0.000 description 5
- 206010070834 Sensitisation Diseases 0.000 description 5
- 238000002512 chemotherapy Methods 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 238000007912 intraperitoneal administration Methods 0.000 description 5
- 229960004194 lidocaine Drugs 0.000 description 5
- 239000003589 local anesthetic agent Substances 0.000 description 5
- 230000033001 locomotion Effects 0.000 description 5
- 210000003141 lower extremity Anatomy 0.000 description 5
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 5
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 5
- 230000002085 persistent effect Effects 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 230000035935 pregnancy Effects 0.000 description 5
- 238000012552 review Methods 0.000 description 5
- 230000000630 rising effect Effects 0.000 description 5
- 230000008313 sensitization Effects 0.000 description 5
- 210000002027 skeletal muscle Anatomy 0.000 description 5
- 231100000331 toxic Toxicity 0.000 description 5
- 230000002588 toxic effect Effects 0.000 description 5
- 230000008673 vomiting Effects 0.000 description 5
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 4
- 101000654356 Homo sapiens Sodium channel protein type 10 subunit alpha Proteins 0.000 description 4
- 206010021118 Hypotonia Diseases 0.000 description 4
- 238000012449 Kunming mouse Methods 0.000 description 4
- XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 description 4
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 4
- 208000001431 Psychomotor Agitation Diseases 0.000 description 4
- 206010038743 Restlessness Diseases 0.000 description 4
- 101710134422 Sodium channel protein type 10 subunit alpha Proteins 0.000 description 4
- 241001441724 Tetraodontidae Species 0.000 description 4
- 206010044565 Tremor Diseases 0.000 description 4
- 239000003708 ampul Substances 0.000 description 4
- 230000000692 anti-sense effect Effects 0.000 description 4
- 230000036772 blood pressure Effects 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- USXKBURXVCBLKJ-UHFFFAOYSA-N chiridquitoxin Chemical compound C12C(O)N=C(N)NC2(C2O)C(O)C3C(C(O)C(N)C(O)=O)(O)C1OC2(O)O3 USXKBURXVCBLKJ-UHFFFAOYSA-N 0.000 description 4
- 210000000349 chromosome Anatomy 0.000 description 4
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 4
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 4
- 230000001976 improved effect Effects 0.000 description 4
- 230000036640 muscle relaxation Effects 0.000 description 4
- 230000003505 mutagenic effect Effects 0.000 description 4
- 231100000150 mutagenicity / genotoxicity testing Toxicity 0.000 description 4
- 230000003040 nociceptive effect Effects 0.000 description 4
- 229960002275 pentobarbital sodium Drugs 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000007958 sleep Effects 0.000 description 4
- 210000000278 spinal cord Anatomy 0.000 description 4
- 230000001629 suppression Effects 0.000 description 4
- 230000001550 time effect Effects 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 230000004580 weight loss Effects 0.000 description 4
- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 description 3
- 206010001497 Agitation Diseases 0.000 description 3
- 208000008035 Back Pain Diseases 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- 241000700198 Cavia Species 0.000 description 3
- 241000700199 Cavia porcellus Species 0.000 description 3
- 206010010904 Convulsion Diseases 0.000 description 3
- 206010020565 Hyperaemia Diseases 0.000 description 3
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 3
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 3
- 208000018142 Leiomyosarcoma Diseases 0.000 description 3
- 208000000114 Pain Threshold Diseases 0.000 description 3
- 206010033799 Paralysis Diseases 0.000 description 3
- 206010035039 Piloerection Diseases 0.000 description 3
- 208000015634 Rectal Neoplasms Diseases 0.000 description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 description 3
- 108010053752 Voltage-Gated Sodium Channels Proteins 0.000 description 3
- 102000016913 Voltage-Gated Sodium Channels Human genes 0.000 description 3
- 208000020560 abdominal swelling Diseases 0.000 description 3
- 229940035674 anesthetics Drugs 0.000 description 3
- 230000004596 appetite loss Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 229960001948 caffeine Drugs 0.000 description 3
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 3
- 238000002591 computed tomography Methods 0.000 description 3
- 230000036461 convulsion Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000005021 gait Effects 0.000 description 3
- 206010017758 gastric cancer Diseases 0.000 description 3
- 239000003193 general anesthetic agent Substances 0.000 description 3
- 229960001680 ibuprofen Drugs 0.000 description 3
- 230000002779 inactivation Effects 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 238000002690 local anesthesia Methods 0.000 description 3
- 229960005015 local anesthetics Drugs 0.000 description 3
- 208000019017 loss of appetite Diseases 0.000 description 3
- 235000021266 loss of appetite Nutrition 0.000 description 3
- 210000001165 lymph node Anatomy 0.000 description 3
- 229960001797 methadone Drugs 0.000 description 3
- 230000037230 mobility Effects 0.000 description 3
- 230000003533 narcotic effect Effects 0.000 description 3
- 230000007830 nerve conduction Effects 0.000 description 3
- 230000002981 neuropathic effect Effects 0.000 description 3
- 239000002581 neurotoxin Substances 0.000 description 3
- 231100000618 neurotoxin Toxicity 0.000 description 3
- 210000001331 nose Anatomy 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000037040 pain threshold Effects 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 230000005371 pilomotor reflex Effects 0.000 description 3
- 210000001747 pupil Anatomy 0.000 description 3
- 206010038038 rectal cancer Diseases 0.000 description 3
- 201000001275 rectum cancer Diseases 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 210000002345 respiratory system Anatomy 0.000 description 3
- 230000035807 sensation Effects 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 230000001235 sensitizing effect Effects 0.000 description 3
- 210000001044 sensory neuron Anatomy 0.000 description 3
- 230000004622 sleep time Effects 0.000 description 3
- 206010041232 sneezing Diseases 0.000 description 3
- 201000011549 stomach cancer Diseases 0.000 description 3
- 230000008961 swelling Effects 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 230000003390 teratogenic effect Effects 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 239000003053 toxin Substances 0.000 description 3
- 231100000765 toxin Toxicity 0.000 description 3
- 108700012359 toxins Proteins 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 206010006784 Burning sensation Diseases 0.000 description 2
- 101100084990 Caenorhabditis elegans rpn-3 gene Proteins 0.000 description 2
- 206010008805 Chromosomal abnormalities Diseases 0.000 description 2
- 206010011703 Cyanosis Diseases 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 206010019233 Headaches Diseases 0.000 description 2
- JAQUASYNZVUNQP-USXIJHARSA-N Levorphanol Chemical compound C1C2=CC=C(O)C=C2[C@]23CCN(C)[C@H]1[C@@H]2CCCC3 JAQUASYNZVUNQP-USXIJHARSA-N 0.000 description 2
- 208000008930 Low Back Pain Diseases 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 208000007101 Muscle Cramp Diseases 0.000 description 2
- 238000011887 Necropsy Methods 0.000 description 2
- 206010028851 Necrosis Diseases 0.000 description 2
- 208000028389 Nerve injury Diseases 0.000 description 2
- CFMYXEVWODSLAX-PZKHIREQSA-N O([C@@]([C@H]1O)(O)O[C@H]2[C@@]3(O)CO)[C@H]3[C@@H](O)[C@]11[C@H]2[C@H](O)N=C(N)N1 Chemical compound O([C@@]([C@H]1O)(O)O[C@H]2[C@@]3(O)CO)[C@H]3[C@@H](O)[C@]11[C@H]2[C@H](O)N=C(N)N1 CFMYXEVWODSLAX-PZKHIREQSA-N 0.000 description 2
- 102000003840 Opioid Receptors Human genes 0.000 description 2
- 108090000137 Opioid Receptors Proteins 0.000 description 2
- UQCNKQCJZOAFTQ-ISWURRPUSA-N Oxymorphone Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O UQCNKQCJZOAFTQ-ISWURRPUSA-N 0.000 description 2
- 208000005374 Poisoning Diseases 0.000 description 2
- 208000004550 Postoperative Pain Diseases 0.000 description 2
- 208000008630 Sialorrhea Diseases 0.000 description 2
- 208000005392 Spasm Diseases 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 230000003187 abdominal effect Effects 0.000 description 2
- 230000001133 acceleration Effects 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000002567 autonomic effect Effects 0.000 description 2
- 230000008335 axon cargo transport Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 210000002798 bone marrow cell Anatomy 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 210000000621 bronchi Anatomy 0.000 description 2
- 229960000623 carbamazepine Drugs 0.000 description 2
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 229960003920 cocaine Drugs 0.000 description 2
- 229960004126 codeine Drugs 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 210000002249 digestive system Anatomy 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 238000005558 fluorometry Methods 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 230000009931 harmful effect Effects 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 230000002489 hematologic effect Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 210000000548 hind-foot Anatomy 0.000 description 2
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 2
- 230000000917 hyperalgesic effect Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000035987 intoxication Effects 0.000 description 2
- 231100000566 intoxication Toxicity 0.000 description 2
- 229960003406 levorphanol Drugs 0.000 description 2
- 231100000861 limb weakness Toxicity 0.000 description 2
- 208000027905 limb weakness Diseases 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 210000005265 lung cell Anatomy 0.000 description 2
- 206010028320 muscle necrosis Diseases 0.000 description 2
- 231100000219 mutagenic Toxicity 0.000 description 2
- 239000003471 mutagenic agent Substances 0.000 description 2
- 231100000707 mutagenic chemical Toxicity 0.000 description 2
- UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 description 2
- 229960004127 naloxone Drugs 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 230000008035 nerve activity Effects 0.000 description 2
- 230000008764 nerve damage Effects 0.000 description 2
- 210000004126 nerve fiber Anatomy 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 238000011587 new zealand white rabbit Methods 0.000 description 2
- 231100000862 numbness Toxicity 0.000 description 2
- 239000003402 opiate agonist Substances 0.000 description 2
- 230000008058 pain sensation Effects 0.000 description 2
- 229960005489 paracetamol Drugs 0.000 description 2
- 208000035824 paresthesia Diseases 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 230000008447 perception Effects 0.000 description 2
- 210000000578 peripheral nerve Anatomy 0.000 description 2
- 210000002856 peripheral neuron Anatomy 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 231100000572 poisoning Toxicity 0.000 description 2
- 230000000607 poisoning effect Effects 0.000 description 2
- 210000004044 posterior horn cell Anatomy 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 210000003314 quadriceps muscle Anatomy 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 210000004994 reproductive system Anatomy 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 230000036387 respiratory rate Effects 0.000 description 2
- 238000006748 scratching Methods 0.000 description 2
- 230000002393 scratching effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 229940125794 sodium channel blocker Drugs 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 238000012353 t test Methods 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- RZEZZMTUAUQGFF-UHFFFAOYSA-N tetrodaminotoxin Chemical compound OC1C(C2O)OC3(O)OC2C2C(N)N=C(N)NC21C3(O)CO RZEZZMTUAUQGFF-UHFFFAOYSA-N 0.000 description 2
- 230000000451 tissue damage Effects 0.000 description 2
- 231100000827 tissue damage Toxicity 0.000 description 2
- 208000004371 toothache Diseases 0.000 description 2
- 230000008791 toxic response Effects 0.000 description 2
- 231100000041 toxicology testing Toxicity 0.000 description 2
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- 239000005526 vasoconstrictor agent Substances 0.000 description 2
- 210000001835 viscera Anatomy 0.000 description 2
- VLPIATFUUWWMKC-SNVBAGLBSA-N (2r)-1-(2,6-dimethylphenoxy)propan-2-amine Chemical compound C[C@@H](N)COC1=C(C)C=CC=C1C VLPIATFUUWWMKC-SNVBAGLBSA-N 0.000 description 1
- FMNQRUKVXAQEAZ-JNRFBPFXSA-N (5z,8s,9r,10e,12s)-9,12-dihydroxy-8-[(1s)-1-hydroxy-3-oxopropyl]heptadeca-5,10-dienoic acid Chemical compound CCCCC[C@H](O)\C=C\[C@@H](O)[C@H]([C@@H](O)CC=O)C\C=C/CCCC(O)=O FMNQRUKVXAQEAZ-JNRFBPFXSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- TVYLLZQTGLZFBW-ZBFHGGJFSA-N (R,R)-tramadol Chemical compound COC1=CC=CC([C@]2(O)[C@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-ZBFHGGJFSA-N 0.000 description 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- JCIIKRHCWVHVFF-UHFFFAOYSA-N 1,2,4-thiadiazol-5-amine;hydrochloride Chemical compound Cl.NC1=NC=NS1 JCIIKRHCWVHVFF-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 102000012440 Acetylcholinesterase Human genes 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 238000010953 Ames test Methods 0.000 description 1
- 231100000039 Ames test Toxicity 0.000 description 1
- 241000269350 Anura Species 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 241000238582 Artemia Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010061728 Bone lesion Diseases 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 206010008531 Chills Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010053398 Clonic convulsion Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 206010011469 Crying Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 229920004937 Dexon® Polymers 0.000 description 1
- 206010013642 Drooling Diseases 0.000 description 1
- 206010013754 Drug withdrawal syndrome Diseases 0.000 description 1
- 208000027534 Emotional disease Diseases 0.000 description 1
- 206010015946 Eye irritation Diseases 0.000 description 1
- 206010017076 Fracture Diseases 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 206010019705 Hepatic pain Diseases 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- 101000583581 Homo sapiens Polyhomeotic-like protein 3 Proteins 0.000 description 1
- 206010020591 Hypercapnia Diseases 0.000 description 1
- 208000008454 Hyperhidrosis Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010065390 Inflammatory pain Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 206010023644 Lacrimation increased Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000036631 Metastatic pain Diseases 0.000 description 1
- 208000034819 Mobility Limitation Diseases 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 208000029549 Muscle injury Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010056677 Nerve degeneration Diseases 0.000 description 1
- 206010029240 Neuritis Diseases 0.000 description 1
- 101100473185 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) rpn-1 gene Proteins 0.000 description 1
- 101710138657 Neurotoxin Proteins 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 239000008896 Opium Substances 0.000 description 1
- BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000282373 Panthera pardus Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102100030905 Polyhomeotic-like protein 3 Human genes 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 241001282135 Poromitra oscitans Species 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 241000269622 Salamandridae Species 0.000 description 1
- 206010039424 Salivary hypersecretion Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 206010040030 Sensory loss Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 101710169783 Spheroidin Proteins 0.000 description 1
- 208000010040 Sprains and Strains Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 241001505535 Taricha torosa Species 0.000 description 1
- 206010043275 Teratogenicity Diseases 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical class NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 206010048232 Yawning Diseases 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 208000028752 abnormal posture Diseases 0.000 description 1
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 201000005179 adrenal carcinoma Diseases 0.000 description 1
- 201000005188 adrenal gland cancer Diseases 0.000 description 1
- 210000003766 afferent neuron Anatomy 0.000 description 1
- 230000008484 agonism Effects 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- IVHKZGYFKJRXBD-UHFFFAOYSA-N amino carbamate Chemical class NOC(N)=O IVHKZGYFKJRXBD-UHFFFAOYSA-N 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 229940124326 anaesthetic agent Drugs 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- IYNDLOXRXUOGIU-LQDWTQKMSA-M benzylpenicillin potassium Chemical compound [K+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)CC1=CC=CC=C1 IYNDLOXRXUOGIU-LQDWTQKMSA-M 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 210000001217 buttock Anatomy 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 229960001747 cinchocaine Drugs 0.000 description 1
- PUFQVTATUTYEAL-UHFFFAOYSA-N cinchocaine Chemical compound C1=CC=CC2=NC(OCCCC)=CC(C(=O)NCCN(CC)CC)=C21 PUFQVTATUTYEAL-UHFFFAOYSA-N 0.000 description 1
- 230000009194 climbing Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000009193 crawling Effects 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000000254 damaging effect Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 229960002069 diamorphine Drugs 0.000 description 1
- 229940097896 diazepam 5 mg Drugs 0.000 description 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000007831 electrophysiology Effects 0.000 description 1
- 238000002001 electrophysiology Methods 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 201000005619 esophageal carcinoma Diseases 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 231100000013 eye irritation Toxicity 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 description 1
- 229960002428 fentanyl Drugs 0.000 description 1
- 231100001048 fetal toxicity Toxicity 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 238000011597 hartley guinea pig Methods 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- WVLOADHCBXTIJK-YNHQPCIGSA-N hydromorphone Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WVLOADHCBXTIJK-YNHQPCIGSA-N 0.000 description 1
- 229960001410 hydromorphone Drugs 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 230000002102 hyperpolarization Effects 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000002642 intravenous therapy Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 230000009191 jumping Effects 0.000 description 1
- 230000004317 lacrimation Effects 0.000 description 1
- 230000006651 lactation Effects 0.000 description 1
- 210000002414 leg Anatomy 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 238000011542 limb amputation Methods 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000036244 malformation Effects 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 230000015654 memory Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000006996 mental state Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 description 1
- 229960003404 mexiletine Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 229960005195 morphine hydrochloride Drugs 0.000 description 1
- XELXKCKNPPSFNN-BJWPBXOKSA-N morphine hydrochloride trihydrate Chemical compound O.O.O.Cl.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O XELXKCKNPPSFNN-BJWPBXOKSA-N 0.000 description 1
- 102000051367 mu Opioid Receptors Human genes 0.000 description 1
- 208000013465 muscle pain Diseases 0.000 description 1
- 231100000299 mutagenicity Toxicity 0.000 description 1
- 230000007886 mutagenicity Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- SBOJXQVPLKSXOG-UHFFFAOYSA-N o-amino-hydroxylamine Chemical class NON SBOJXQVPLKSXOG-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 229960001027 opium Drugs 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 229940051877 other opioids in atc Drugs 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229960002085 oxycodone Drugs 0.000 description 1
- 229960005118 oxymorphone Drugs 0.000 description 1
- 230000037325 pain tolerance Effects 0.000 description 1
- 238000010422 painting Methods 0.000 description 1
- 235000007183 paleface Nutrition 0.000 description 1
- 230000001769 paralizing effect Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- VOKSWYLNZZRQPF-GDIGMMSISA-N pentazocine Chemical compound C1C2=CC=C(O)C=C2[C@@]2(C)[C@@H](C)[C@@H]1N(CC=C(C)C)CC2 VOKSWYLNZZRQPF-GDIGMMSISA-N 0.000 description 1
- 229960005301 pentazocine Drugs 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 229940011964 pentobarbital sodium 30 mg Drugs 0.000 description 1
- 210000003200 peritoneal cavity Anatomy 0.000 description 1
- WCNLCIJMFAJCPX-UHFFFAOYSA-N pethidine hydrochloride Chemical compound Cl.C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 WCNLCIJMFAJCPX-UHFFFAOYSA-N 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000079 pharmacotherapeutic effect Effects 0.000 description 1
- 238000001050 pharmacotherapy Methods 0.000 description 1
- 229940096826 phenylmercuric acetate Drugs 0.000 description 1
- PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229960001896 pramocaine Drugs 0.000 description 1
- DQKXQSGTHWVTAD-UHFFFAOYSA-N pramocaine Chemical compound C1=CC(OCCCC)=CC=C1OCCCN1CCOCC1 DQKXQSGTHWVTAD-UHFFFAOYSA-N 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- STHAHFPLLHRRRO-UHFFFAOYSA-N propipocaine Chemical compound C1=CC(OCCC)=CC=C1C(=O)CCN1CCCCC1 STHAHFPLLHRRRO-UHFFFAOYSA-N 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 210000003019 respiratory muscle Anatomy 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 230000028527 righting reflex Effects 0.000 description 1
- 210000003497 sciatic nerve Anatomy 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 230000020341 sensory perception of pain Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 230000009528 severe injury Effects 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 208000010485 smooth muscle tumor Diseases 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- BHZOKUMUHVTPBX-UHFFFAOYSA-M sodium acetic acid acetate Chemical compound [Na+].CC(O)=O.CC([O-])=O BHZOKUMUHVTPBX-UHFFFAOYSA-M 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- QCZWKLBJYRVKPW-LYWCOASQSA-N spheroidene Natural products COC(C)(C)CC=CC(=CC=CC(=CC=CC(=CC=CC=CC(C)C=C/C=C(C)/CCC=C(/C)CC=C(C)C)C)C)C QCZWKLBJYRVKPW-LYWCOASQSA-N 0.000 description 1
- 210000001562 sternum Anatomy 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 231100000211 teratogenicity Toxicity 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 210000003371 toe Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960004380 tramadol Drugs 0.000 description 1
- TVYLLZQTGLZFBW-GOEBONIOSA-N tramadol Natural products COC1=CC=CC([C@@]2(O)[C@@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-GOEBONIOSA-N 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 108020001612 μ-opioid receptors Proteins 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
- A61P23/02—Local anaesthetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Anesthesiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Electrotherapy Devices (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Steroid Compounds (AREA)
- Medicinal Preparation (AREA)
- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Laser Surgery Devices (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB001245171A CN1284536C (zh) | 2000-09-18 | 2000-09-18 | 河豚毒素或蛤蚌毒素及其类似物在制备用于全身镇痛的镇痛药中的应用 |
| PCT/CN2001/001391 WO2002022129A1 (en) | 2000-09-18 | 2001-09-11 | A method of analgesia |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2004508404A true JP2004508404A (ja) | 2004-03-18 |
| JP2004508404A5 JP2004508404A5 (enExample) | 2008-11-06 |
Family
ID=4590472
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002526380A Abandoned JP2004508404A (ja) | 2000-09-18 | 2001-09-11 | 鎮痛手法 |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US6407088B1 (enExample) |
| EP (3) | EP2298306B1 (enExample) |
| JP (1) | JP2004508404A (enExample) |
| KR (2) | KR100891568B1 (enExample) |
| CN (1) | CN1284536C (enExample) |
| AT (2) | ATE542534T1 (enExample) |
| AU (1) | AU2002213785A1 (enExample) |
| BG (1) | BG107690A (enExample) |
| BR (1) | BR0113961A (enExample) |
| CA (1) | CA2421562C (enExample) |
| DE (1) | DE60140466D1 (enExample) |
| EA (1) | EA004870B1 (enExample) |
| EE (1) | EE200300106A (enExample) |
| ES (1) | ES2435463T3 (enExample) |
| HR (1) | HRP20030202A2 (enExample) |
| HU (1) | HUP0302677A3 (enExample) |
| IL (1) | IL154342A0 (enExample) |
| IS (1) | IS6719A (enExample) |
| MX (1) | MXPA03002389A (enExample) |
| NO (1) | NO323960B1 (enExample) |
| PL (1) | PL360616A1 (enExample) |
| SK (1) | SK3732003A3 (enExample) |
| UA (1) | UA76960C2 (enExample) |
| WO (1) | WO2002022129A1 (enExample) |
| YU (1) | YU17103A (enExample) |
| ZA (1) | ZA200301852B (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007538010A (ja) * | 2004-05-07 | 2007-12-27 | ファイトトックス リミテッド | フィコトキシンの経皮投与 |
| JP2013519653A (ja) * | 2010-02-10 | 2013-05-30 | ファイトトックス リミテッド | サキシトキシン誘導体での触覚の喪失の処置 |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE289295T1 (de) | 1997-04-22 | 2005-03-15 | Euro Celtique Sa | Die verwendung von durch carbozyklische und heterozyklische reste substituierte semicarbazonen und thiosemicarbazonen als natriumkanalblocker |
| CN1236773C (zh) | 2000-11-22 | 2006-01-18 | 南宁枫叶药业有限公司 | 用于镇痛、麻醉或治疗药物依赖性的制剂 |
| US7119062B1 (en) | 2001-02-23 | 2006-10-10 | Neucoll, Inc. | Methods and compositions for improved articular surgery using collagen |
| CN1269482C (zh) * | 2001-05-18 | 2006-08-16 | 威克斯医药有限公司 | 钠离子通道阻断剂和阿片类镇痛剂在制备用于对哺乳动物进行协同镇痛的药物中的应用 |
| CN1203860C (zh) * | 2001-06-22 | 2005-06-01 | 威克斯医药有限公司 | 钠离子通道阻断剂和阿司匹林在制备用于对哺乳动物进行协同镇痛的药物中的应用 |
| MXPA04004543A (es) | 2001-11-15 | 2005-03-31 | Micro Algae Corp | Composiciones farmaceuticas que contienen 3,4-propinoperhidropurinas y sus usos para el bloqueo de la transmision neuronal. |
| AU2003250128A1 (en) * | 2002-08-01 | 2004-02-23 | Bayer Healthcare Ag | Diagnostics and therapeutics for diseases associated with g-protein coupled receptor 37 (gpr37) |
| AU2004207010A1 (en) * | 2003-01-30 | 2004-08-12 | Dynogen Pharmaceuticals, Inc. | Methods of treating lower urinary tract disorders using sodium channel modulators |
| CN1568999A (zh) | 2003-07-14 | 2005-01-26 | 南宁枫叶药业有限公司 | 稳定的医药用河豚毒素冷冻干燥制剂 |
| JP2005154368A (ja) * | 2003-11-27 | 2005-06-16 | Teikoku Seiyaku Co Ltd | ジソピラミド含有神経因性疼痛の鎮痛剤 |
| BRPI0510759A (pt) * | 2004-05-07 | 2007-11-20 | Phytotox Ltd | método de facilitar a cura de um ferimento |
| US20050282836A1 (en) * | 2004-06-22 | 2005-12-22 | Weiyang Lin | Solid orally ingestible formulations of tetrodotoxin |
| US20060034823A1 (en) * | 2004-08-13 | 2006-02-16 | Paul Reid | Method of production and use of crotoxin as an analgesic |
| CN100363006C (zh) * | 2004-08-20 | 2008-01-23 | 厦门朝阳生物工程有限公司 | 一种戒毒制剂及其制备方法 |
| AU2005287511A1 (en) * | 2004-09-21 | 2006-03-30 | Wex Medical Limited | Tetrodotoxin and its derivatives for the treatment of central-nervously derived neuropathic pain |
| KR20070092698A (ko) * | 2004-09-22 | 2007-09-13 | 라보라토리오스 델 드라. 에스테브.에스.에이. | 말초 신경적으로 유발된 신경병증성 통증을 치료하기 위한테트로도톡신 및 그것의 유도체 |
| EP1714655A1 (en) * | 2005-04-22 | 2006-10-25 | Laboratorios Del Dr. Esteve, S.A. | Use of sodium channel blockers and their analogues for the treatment of nicotine dependency |
| WO2006084765A1 (en) * | 2005-02-11 | 2006-08-17 | Wex Pharmaceuticals, Inc. | Use of sodium channel blockers and their analogues for the treatment of nicotine dependency |
| EP1690541A1 (en) * | 2005-02-11 | 2006-08-16 | Laboratorios Del Dr. Esteve, S.A. | Use of a sodium channel blocker and their analogues for the treatment of nicotine dependency |
| EP1702627A1 (en) * | 2005-03-18 | 2006-09-20 | Laboratorios Del Dr. Esteve, S.A. | Analgesic combination of sodium channel blockers with opioid antagonists |
| CA2619668A1 (en) * | 2005-08-25 | 2007-03-01 | Edge Renfeng Wang | Use of sodium channel blockers for the management of musculoskeletal pain |
| US20100144767A1 (en) * | 2005-08-25 | 2010-06-10 | Wex Pharmaceuticals, Inc. | Use of sodium channel blockers for the treatment of visceral pain or pain caused by cancer treatment |
| US20070148159A1 (en) * | 2005-12-22 | 2007-06-28 | Reid Paul F | Use of crotoxin as an analgesic - CIP |
| GB0603008D0 (en) * | 2006-02-14 | 2006-03-29 | Portela & Ca Sa | Method |
| EP1844781A1 (en) | 2006-02-22 | 2007-10-17 | Wex Pharmaceuticals Inc. | Use of sodium channel blockers for the treatment of preterm labor |
| WO2007110220A1 (en) * | 2006-03-27 | 2007-10-04 | Wex Pharmaceuticals Inc. | USE OF 4,9-ANHYDRO-TETRODOTOXIN FOR THE TREATMENT OF DISEASES RELATED TO THE VOLTAGE-GATED SODIUM CHANNEL α SUBUNIT NAV 1.6 |
| EP1844782A1 (en) * | 2006-03-27 | 2007-10-17 | Wex Pharmaceuticals, Inc | Use of 4,9-anhydro-tetrodotoxin for the treatment of diseases related to the voltage-gated sodium channel subunit Nav1.6 |
| EP1844783A1 (en) * | 2006-03-27 | 2007-10-17 | Wex Pharmaceuticals, Inc | Use of 4,9-anhydro-tetrodotoxin for the treatment of diseases related to the voltage-gated sodium channel - subunit Nav1.6 |
| WO2007110221A1 (en) * | 2006-03-27 | 2007-10-04 | Wex Pharmaceuticals Inc. | Use of sodium channel blockers for the treatment of neuropathic pain developing as a consequence of chemotherapy |
| CN100438873C (zh) * | 2006-06-26 | 2008-12-03 | 黄致强 | 将河鲀毒素作为镇痛药的耐受抑制剂在制备复方镇痛制剂中的应用 |
| EP1882692A1 (en) * | 2006-07-28 | 2008-01-30 | Wex Pharmaceuticals Inc. | Dimethano-[1,3]dioxocino[6,5-D]pyrimidine-spiro derivatives of tetrodotoxin, process for their synthesis and uses thereof in the treatment of pain |
| EP2173167A4 (en) * | 2007-07-06 | 2010-07-28 | Nuon Therapeutics Inc | TREATMENT OF NEUROPATHIC PAIN |
| CN101352422B (zh) * | 2008-09-17 | 2011-04-20 | 厦门朝阳生物工程有限公司 | 河豚毒素冻干粉针制剂及其制备方法 |
| US8952152B2 (en) | 2009-03-24 | 2015-02-10 | Proteus S.A. | Methods for purifying phycotoxins, pharmaceutical compositions containing purified phycotoxins, and methods of use thereof |
| US20120034296A1 (en) * | 2009-04-08 | 2012-02-09 | Massachusetts Institute Of Technology | Prolonged duration local anesthesia with minimal toxicity |
| US20120310140A1 (en) | 2010-12-01 | 2012-12-06 | Spinal Modulation, Inc. | Directed delivery of agents to neural anatomy |
| AU2014240392A1 (en) | 2013-03-14 | 2015-11-05 | Regeneron Pharmaceuticals, Inc. | Human antibodies to Nav1.7 |
| KR102787826B1 (ko) | 2013-03-15 | 2025-03-31 | 더 칠드런스 메디칼 센터 코포레이션 | 지속성 국소 마취용 네오삭시톡신 조합 제형 |
| US8986694B1 (en) | 2014-07-15 | 2015-03-24 | Kymab Limited | Targeting human nav1.7 variants for treatment of pain |
| US8992927B1 (en) | 2014-07-15 | 2015-03-31 | Kymab Limited | Targeting human NAV1.7 variants for treatment of pain |
| GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
| US9139653B1 (en) | 2015-04-30 | 2015-09-22 | Kymab Limited | Anti-human OX40L antibodies and methods of treatment |
| KR102379464B1 (ko) | 2016-06-20 | 2022-03-29 | 키맵 리미티드 | 항-pd-l1 항체 |
| WO2018083248A1 (en) | 2016-11-03 | 2018-05-11 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses & methods |
| CN107198689A (zh) * | 2017-07-11 | 2017-09-26 | 东新皓特（北京）生化科技有限公司 | 用于治疗疼痛病症的河豚毒素药物组合物及外用药 |
| EP4326282A4 (en) | 2021-04-23 | 2025-02-26 | Wex Pharmaceuticals Inc. | Tetrodotoxin liquid formulations |
| MX2024001877A (es) | 2021-08-10 | 2024-02-28 | Kymab Ltd | Tratamiento de dermatitis atopica. |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4022899A (en) | 1973-06-12 | 1977-05-10 | Astra Pharmaceutical Products, Inc. | Synergistic local anesthetic compositions |
| US4029793A (en) | 1973-06-12 | 1977-06-14 | Astra Pharmaceutical Products, Inc. | Synergistic local anesthetic compositions |
| AU1888195A (en) * | 1994-03-17 | 1995-10-03 | Nanning Maple Leaf Pharmaceutical Co. Ltd. | The use of amino hydrogenated quinazoline compounds and derivatives thereof for abstaining from drug dependence |
| CN1072486C (zh) * | 1996-09-24 | 2001-10-10 | 王维国 | 用于戒毒、镇痛的药剂及其制法 |
| US6030974A (en) * | 1997-04-02 | 2000-02-29 | The Regents Of The University Of California | Method of anesthesia |
| AU7389098A (en) * | 1997-05-16 | 1998-12-08 | Brigham And Women's Hospital | Local anesthetic formulations |
| CN1236773C (zh) * | 2000-11-22 | 2006-01-18 | 南宁枫叶药业有限公司 | 用于镇痛、麻醉或治疗药物依赖性的制剂 |
| CN1269482C (zh) * | 2001-05-18 | 2006-08-16 | 威克斯医药有限公司 | 钠离子通道阻断剂和阿片类镇痛剂在制备用于对哺乳动物进行协同镇痛的药物中的应用 |
-
2000
- 2000-09-18 CN CNB001245171A patent/CN1284536C/zh not_active Expired - Lifetime
- 2000-10-25 US US09/695,053 patent/US6407088B1/en not_active Expired - Lifetime
-
2001
- 2001-09-11 AT AT04022073T patent/ATE542534T1/de active
- 2001-09-11 EE EEP200300106A patent/EE200300106A/xx unknown
- 2001-09-11 IL IL15434201A patent/IL154342A0/xx unknown
- 2001-09-11 AT AT01982091T patent/ATE447959T1/de not_active IP Right Cessation
- 2001-09-11 JP JP2002526380A patent/JP2004508404A/ja not_active Abandoned
- 2001-09-11 CA CA2421562A patent/CA2421562C/en not_active Expired - Lifetime
- 2001-09-11 PL PL36061601A patent/PL360616A1/xx unknown
- 2001-09-11 HU HU0302677A patent/HUP0302677A3/hu unknown
- 2001-09-11 WO PCT/CN2001/001391 patent/WO2002022129A1/en not_active Ceased
- 2001-09-11 AU AU2002213785A patent/AU2002213785A1/en not_active Abandoned
- 2001-09-11 SK SK373-2003A patent/SK3732003A3/sk unknown
- 2001-09-11 EP EP10180006.8A patent/EP2298306B1/en not_active Expired - Lifetime
- 2001-09-11 DE DE60140466T patent/DE60140466D1/de not_active Expired - Lifetime
- 2001-09-11 HR HR20030202A patent/HRP20030202A2/hr not_active Application Discontinuation
- 2001-09-11 MX MXPA03002389A patent/MXPA03002389A/es active IP Right Grant
- 2001-09-11 KR KR1020037003723A patent/KR100891568B1/ko not_active Expired - Lifetime
- 2001-09-11 YU YU17103A patent/YU17103A/sh unknown
- 2001-09-11 EP EP04022073A patent/EP1563839B1/en not_active Expired - Lifetime
- 2001-09-11 ES ES10180006T patent/ES2435463T3/es not_active Expired - Lifetime
- 2001-09-11 EP EP01982091A patent/EP1320369B1/en not_active Expired - Lifetime
- 2001-09-11 BR BR0113961-4A patent/BR0113961A/pt not_active IP Right Cessation
- 2001-09-11 EA EA200300172A patent/EA004870B1/ru unknown
- 2001-09-11 KR KR1020077023825A patent/KR20070112864A/ko not_active Withdrawn
- 2001-11-09 UA UA2003032528A patent/UA76960C2/uk unknown
-
2003
- 2003-02-14 IS IS6719A patent/IS6719A/is unknown
- 2003-02-27 NO NO20030915A patent/NO323960B1/no unknown
- 2003-03-06 ZA ZA200301852A patent/ZA200301852B/en unknown
- 2003-03-31 BG BG107690A patent/BG107690A/bg unknown
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007538010A (ja) * | 2004-05-07 | 2007-12-27 | ファイトトックス リミテッド | フィコトキシンの経皮投与 |
| JP2013519653A (ja) * | 2010-02-10 | 2013-05-30 | ファイトトックス リミテッド | サキシトキシン誘導体での触覚の喪失の処置 |
| US9107925B2 (en) | 2010-02-10 | 2015-08-18 | Phytotox Limited | Sodium channel blocker for treatment of loss of superficial sensitivity |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6407088B1 (en) | Method of analgesia | |
| US8680076B2 (en) | Methods of treatment, improvement and prevention using haloaryl substituted aminopurines | |
| CN115745890B (zh) | 一种酯键化合物及其制备方法和应用、镇痛药物 | |
| CN108686023A (zh) | 一种治疗老年性皮肤瘙痒的止痒润肤精油 | |
| WO2022253034A1 (zh) | 吡咯并嘧啶类化合物的用途 | |
| EA008339B1 (ru) | Способы лечения пациентов, страдающих синдромом усталых ног или связанными с ним заболеваниями | |
| EP3769759A1 (en) | Epilepsy treatment agent | |
| CA3247370A1 (en) | COMPOUNDS AND METHODS OF TREATMENT FOR SPASTICITY | |
| CN110279691B (zh) | 一种外科术后护理镇痛药物及其用途 | |
| CN112569237B (zh) | 伊马替尼及其衍生物与尼古丁或其类似物联用或复方在防治尼古丁成瘾与复吸中的应用 | |
| KR20070018015A (ko) | 척수 손상 치료를 위한ｎ-(2-아릴-프로피오닐)-술폰아마이드의 용도 | |
| AU2007200073B2 (en) | A Method of Analgesia | |
| AU2015363757B2 (en) | Diarylmethylidene piperidine derivatives and their use as delta opioid receptor agonists | |
| HK40111957A (en) | Compounds and methods for treating spasticity | |
| TW202519202A (zh) | 3-[(苯並[d][1,3]二氧戊環-4-基)-氧基]-3-芳基丙胺類化合物在製備治療性功能障礙的藥物中的用途 | |
| CN107456454A (zh) | 一种预防或治疗炎性疾病的药物组合物 | |
| EP4277614A1 (en) | Compositions and methods for inducing defecation | |
| WO2021063387A1 (zh) | 伊马替尼及其衍生物的组合物在制备预防、治疗及防治成瘾复吸药物中的应用 | |
| WO2020087685A1 (zh) | 青蒿衍生物在制备抗癫痫药物中的应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080911 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080911 |
|
| A762 | Written abandonment of application |
Free format text: JAPANESE INTERMEDIATE CODE: A762 Effective date: 20110415 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110511 |