JP2004529959A - 鎮痛剤組成物と手法 - Google Patents
鎮痛剤組成物と手法 Download PDFInfo
- Publication number
- JP2004529959A JP2004529959A JP2002590989A JP2002590989A JP2004529959A JP 2004529959 A JP2004529959 A JP 2004529959A JP 2002590989 A JP2002590989 A JP 2002590989A JP 2002590989 A JP2002590989 A JP 2002590989A JP 2004529959 A JP2004529959 A JP 2004529959A
- Authority
- JP
- Japan
- Prior art keywords
- morphine
- opioid
- sodium channel
- ttx
- analgesic
- 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.)
- Pending
Links
- 230000000202 analgesic effect Effects 0.000 title claims abstract description 43
- 239000000203 mixture Substances 0.000 title claims abstract description 13
- 238000000034 method Methods 0.000 title claims description 36
- 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 abstract description 94
- 229950010357 tetrodotoxin Drugs 0.000 claims abstract description 88
- 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 abstract description 88
- 108010052164 Sodium Channels Proteins 0.000 claims abstract description 30
- 102000018674 Sodium Channels Human genes 0.000 claims abstract description 30
- 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 claims abstract description 25
- RPQXVSUAYFXFJA-UHFFFAOYSA-N saxitoxin hydrate Natural products NC(=O)OCC1N=C(N)N2CCC(O)(O)C22NC(N)=NC12 RPQXVSUAYFXFJA-UHFFFAOYSA-N 0.000 claims abstract description 25
- 239000000014 opioid analgesic Substances 0.000 claims abstract description 22
- 150000001875 compounds Chemical class 0.000 claims abstract description 21
- 230000036592 analgesia Effects 0.000 claims abstract description 15
- 241000124008 Mammalia Species 0.000 claims abstract description 8
- 229940079593 drug Drugs 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 6
- 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 claims description 195
- 229960005181 morphine Drugs 0.000 claims description 96
- 230000002195 synergetic effect Effects 0.000 claims description 13
- 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 claims description 10
- 239000003195 sodium channel blocking agent Substances 0.000 claims description 10
- 230000000903 blocking effect Effects 0.000 claims description 9
- 229940125794 sodium channel blocker Drugs 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 7
- 230000037396 body weight Effects 0.000 claims description 6
- 229960002428 fentanyl Drugs 0.000 claims description 6
- 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 claims description 6
- 229960004126 codeine Drugs 0.000 claims description 5
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 claims description 5
- 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 claims description 4
- -1 ethoxytetrodotoxin Chemical compound 0.000 claims description 4
- 229960001797 methadone Drugs 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 6
- 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 1
- 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 1
- 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 1
- 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 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- RZEZZMTUAUQGFF-UHFFFAOYSA-N tetrodaminotoxin Chemical compound OC1C(C2O)OC3(O)OC2C2C(N)N=C(N)NC21C3(O)CO RZEZZMTUAUQGFF-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 208000002193 Pain Diseases 0.000 abstract description 39
- 230000036407 pain Effects 0.000 abstract description 29
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 30
- 241000700159 Rattus Species 0.000 description 27
- 229940005483 opioid analgesics Drugs 0.000 description 21
- 238000012360 testing method Methods 0.000 description 20
- 238000011260 co-administration Methods 0.000 description 14
- 231100000636 lethal dose Toxicity 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 230000004044 response Effects 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 231100000419 toxicity Toxicity 0.000 description 8
- 230000001988 toxicity Effects 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 7
- 230000003993 interaction Effects 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 206010065390 Inflammatory pain Diseases 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 230000001629 suppression Effects 0.000 description 6
- 231100000331 toxic Toxicity 0.000 description 6
- 230000002588 toxic effect Effects 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 108090000137 Opioid Receptors Proteins 0.000 description 5
- 102000003840 Opioid Receptors Human genes 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 208000005298 acute pain Diseases 0.000 description 5
- 230000036749 excitatory postsynaptic potential Effects 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 102000051367 mu Opioid Receptors Human genes 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 210000003594 spinal ganglia Anatomy 0.000 description 5
- 238000005303 weighing Methods 0.000 description 5
- 108020001612 μ-opioid receptors Proteins 0.000 description 5
- SNPXXFHHLSLKNY-UHFFFAOYSA-N (2,6-diamino-10,10-dihydroxy-1-methyl-3a,4,8,9-tetrahydropyrrolo[1,2-c]purin-4-yl) carbamate Chemical compound NC=1N(C23N(C(=NC(C2N1)OC(=O)N)N)CCC3(O)O)C SNPXXFHHLSLKNY-UHFFFAOYSA-N 0.000 description 4
- 208000000094 Chronic Pain Diseases 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- 241000700157 Rattus norvegicus Species 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 229960005195 morphine hydrochloride Drugs 0.000 description 4
- 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 4
- 210000002569 neuron Anatomy 0.000 description 4
- 210000000929 nociceptor Anatomy 0.000 description 4
- 229940127240 opiate Drugs 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 206010012335 Dependence Diseases 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- WPNJAUFVNXKLIM-UHFFFAOYSA-N Moxonidine Chemical compound COC1=NC(C)=NC(Cl)=C1NC1=NCCN1 WPNJAUFVNXKLIM-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 239000000730 antalgic agent Substances 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 239000000835 fiber Substances 0.000 description 3
- 238000010255 intramuscular injection Methods 0.000 description 3
- 239000007927 intramuscular injection Substances 0.000 description 3
- 229960003938 moxonidine Drugs 0.000 description 3
- 230000001473 noxious effect Effects 0.000 description 3
- 230000020341 sensory perception of pain Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 229940095064 tartrate Drugs 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 231100000111 LD50 Toxicity 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 102000016913 Voltage-Gated Sodium Channels Human genes 0.000 description 2
- 108010053752 Voltage-Gated Sodium Channels Proteins 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000001055 chewing effect Effects 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 108700023159 delta Opioid Receptors Proteins 0.000 description 2
- 102000048124 delta Opioid Receptors Human genes 0.000 description 2
- 230000000763 evoking effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002102 hyperpolarization Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 210000002161 motor neuron Anatomy 0.000 description 2
- 108091008700 nociceptors Proteins 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- FWGXLJYMZWCJJV-LJXGPVSSSA-N (4s)-4-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]-3-phenylpropanoyl]amino]-5-[[(2s)-1-[[(2s)-1-(carboxymethylamino)-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O)C(C)C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 FWGXLJYMZWCJJV-LJXGPVSSSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 108700040991 Ala(2)- deltorphin II Proteins 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010058019 Cancer Pain Diseases 0.000 description 1
- 108091006146 Channels Proteins 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
- 206010010774 Constipation Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- NUNBRHVOPFWRRG-RCEFDBTISA-N Deltorphin B Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(=O)N[C@@H](C(C)C)C(=O)NCC(N)=O)C(C)C)NC(=O)[C@@H](C)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 NUNBRHVOPFWRRG-RCEFDBTISA-N 0.000 description 1
- 241001539473 Euphoria Species 0.000 description 1
- 206010015535 Euphoric mood Diseases 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 208000001294 Nociceptive Pain Diseases 0.000 description 1
- 229940127450 Opioid Agonists Drugs 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 208000004550 Postoperative Pain Diseases 0.000 description 1
- 101100244562 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) oprD gene Proteins 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- ZTVQQQVZCWLTDF-UHFFFAOYSA-N Remifentanil Chemical compound C1CN(CCC(=O)OC)CCC1(C(=O)OC)N(C(=O)CC)C1=CC=CC=C1 ZTVQQQVZCWLTDF-UHFFFAOYSA-N 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 206010038678 Respiratory depression Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 230000004665 defense response Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000002461 excitatory amino acid Effects 0.000 description 1
- 239000003257 excitatory amino acid Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 238000002690 local anesthesia Methods 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229940124637 non-opioid analgesic drug Drugs 0.000 description 1
- 229940121367 non-opioid analgesics Drugs 0.000 description 1
- 210000000578 peripheral nerve Anatomy 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
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229960003394 remifentanil Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000026416 response to pain Effects 0.000 description 1
- 210000001044 sensory neuron Anatomy 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000011885 synergistic combination Substances 0.000 description 1
- 230000009044 synergistic interaction Effects 0.000 description 1
- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 210000001170 unmyelinated nerve fiber Anatomy 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- 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
- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine 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)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011180986A CN1269482C (zh) | 2001-05-18 | 2001-05-18 | 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 |
| PCT/CN2002/000339 WO2002094272A1 (en) | 2001-05-18 | 2002-05-20 | Analgesic composition and method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2004529959A true JP2004529959A (ja) | 2004-09-30 |
| JP2004529959A5 JP2004529959A5 (https=) | 2006-01-05 |
Family
ID=4662967
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002590989A Pending JP2004529959A (ja) | 2001-05-18 | 2002-05-20 | 鎮痛剤組成物と手法 |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US6780866B2 (https=) |
| EP (1) | EP1387685B1 (https=) |
| JP (1) | JP2004529959A (https=) |
| CN (1) | CN1269482C (https=) |
| AT (1) | ATE464903T1 (https=) |
| CA (1) | CA2485337C (https=) |
| DE (1) | DE60236077D1 (https=) |
| ES (1) | ES2344631T3 (https=) |
| WO (1) | WO2002094272A1 (https=) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1284536C (zh) * | 2000-09-18 | 2006-11-15 | 威克斯医药有限公司 | 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 |
| 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 |
| 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. |
| 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 |
| 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 |
| JP2007536269A (ja) * | 2004-05-07 | 2007-12-13 | ファイトトックス リミテッド | ゴニオトキシンを用いた創傷の治療方法 |
| CN101039675A (zh) * | 2004-09-22 | 2007-09-19 | 埃斯蒂文博士实验室股份有限公司 | 河豚毒素及其衍生物用于治疗外周神经源性神经痛 |
| EP1702627A1 (en) * | 2005-03-18 | 2006-09-20 | Laboratorios Del Dr. Esteve, S.A. | Analgesic combination of sodium channel blockers with opioid antagonists |
| US20100048592A1 (en) * | 2005-08-25 | 2010-02-25 | Wex Pharmaceuticals Inc. | Use of sodium channel blockers for the management of musculoskeletal pain |
| WO2007025212A2 (en) * | 2005-08-25 | 2007-03-01 | Wex Pharmaceuticals, Inc. | Use of sodium channel blockers for the treatment of visceral pain or pain caused by cancer treatment |
| GB0603008D0 (en) * | 2006-02-14 | 2006-03-29 | Portela & Ca Sa | Method |
| ES2691411T3 (es) | 2006-03-27 | 2018-11-27 | Wex Medical Limited | Uso de bloqueadores de los canales de sodio para el tratamiento del dolor neuropático que se desarrolla como consecuencia de la quimioterapia |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4022899A (en) | 1973-06-12 | 1977-05-10 | Astra Pharmaceutical Products, Inc. | Synergistic local anesthetic compositions |
| US4906779A (en) * | 1986-07-10 | 1990-03-06 | State Of Oregon, Acting By And Through The Oregon State Board Of Higher Education, Acting For And On Behalf Of The Oregon Health Sciences University | N,N'-disubstituted guanidines and their use as excitatory amino acid antagonists |
| US5262568A (en) * | 1990-03-02 | 1993-11-16 | State Of Oregon | Tri- and tetra-substituted guanidines and their use as excitatory amino acid antagonists |
| WO1993013128A1 (en) * | 1991-12-30 | 1993-07-08 | Neurex Corporation | Methods of producing analgesia and enhancing opiate analgesia |
| NZ268969A (en) | 1993-07-23 | 1997-06-24 | Toray Industries | Morphinan derivatives and pharmaceutical compositions |
| WO1995023132A1 (en) * | 1994-02-23 | 1995-08-31 | Cambridge Neuroscience, Inc. | Blockers of ion channels and methods of use thereof |
| 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 |
| GB9513180D0 (en) * | 1995-06-28 | 1995-08-30 | Univ London | Ion channel |
| DE19602970A1 (de) | 1995-12-20 | 1997-07-31 | Nycomed Arzneimittel Gmbh | Neue 7,8- Dihydromorphinderivate, Verfahren zu deren Herstellung und deren Verwendung |
| CN1072486C (zh) * | 1996-09-24 | 2001-10-10 | 王维国 | 用于戒毒、镇痛的药剂及其制法 |
| CN1081034C (zh) * | 1997-03-07 | 2002-03-20 | 潘心富 | 一种双胍基氢化嘌呤环类化合物的戒毒药 |
| WO1998043619A2 (en) * | 1997-04-02 | 1998-10-08 | The Regents Of The University Of California | Method of local anesthesia |
| AU7389098A (en) * | 1997-05-16 | 1998-12-08 | Brigham And Women's Hospital | Local anesthetic formulations |
| DE19936719A1 (de) * | 1999-08-06 | 2001-02-15 | Gruenenthal Gmbh | Substituierte 1,5-Dihydropyrrol-2-on-Derivate |
| CN1284536C (zh) | 2000-09-18 | 2006-11-15 | 威克斯医药有限公司 | 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 |
| CN1203857C (zh) * | 2000-09-18 | 2005-06-01 | 威克斯医药有限公司 | 局部麻醉与镇痛的新方法 |
| 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 |
-
2001
- 2001-05-18 CN CNB011180986A patent/CN1269482C/zh not_active Expired - Fee Related
-
2002
- 2002-02-05 US US10/062,483 patent/US6780866B2/en not_active Expired - Fee Related
- 2002-05-20 DE DE60236077T patent/DE60236077D1/de not_active Expired - Lifetime
- 2002-05-20 WO PCT/CN2002/000339 patent/WO2002094272A1/en not_active Ceased
- 2002-05-20 ES ES02734980T patent/ES2344631T3/es not_active Expired - Lifetime
- 2002-05-20 CA CA002485337A patent/CA2485337C/en not_active Expired - Fee Related
- 2002-05-20 EP EP02734980A patent/EP1387685B1/en not_active Expired - Lifetime
- 2002-05-20 AT AT02734980T patent/ATE464903T1/de not_active IP Right Cessation
- 2002-05-20 JP JP2002590989A patent/JP2004529959A/ja active Pending
-
2004
- 2004-05-20 US US10/849,240 patent/US20040214842A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20040214842A1 (en) | 2004-10-28 |
| CN1386505A (zh) | 2002-12-25 |
| DE60236077D1 (de) | 2010-06-02 |
| EP1387685A1 (en) | 2004-02-11 |
| EP1387685B1 (en) | 2010-04-21 |
| CN1269482C (zh) | 2006-08-16 |
| US6780866B2 (en) | 2004-08-24 |
| US20020198226A1 (en) | 2002-12-26 |
| CA2485337C (en) | 2007-08-28 |
| WO2002094272A1 (en) | 2002-11-28 |
| ES2344631T3 (es) | 2010-09-02 |
| CA2485337A1 (en) | 2002-11-28 |
| EP1387685A4 (en) | 2007-05-23 |
| ATE464903T1 (de) | 2010-05-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2336902C (en) | Topical compositions comprising an opioid analgesic and an nmda antagonist | |
| KR20030060771A (ko) | 국소용 마취제/아편양약물 제제 및 이들의 용도 | |
| JP2007507538A (ja) | 疼痛軽減方法 | |
| JP2003514013A (ja) | 医薬組成物 | |
| JP2004529959A (ja) | 鎮痛剤組成物と手法 | |
| KR20110021823A (ko) | 진통 내성 억제제 | |
| Rizzi et al. | Spinal antinociceptive effects of the novel NOP receptor agonist PWT2‐nociceptin/orphanin FQ in mice and monkeys | |
| JP2021138703A (ja) | オピオイドとｎ−アシルエタノールアミンの組み合わせ | |
| US20150087613A1 (en) | Inhibition of Opioid Antinociceptive Tolerance and Withdrawal in Nociceptive Pain Therapy | |
| Yoon et al. | Additive antinociception between intrathecal sildenafil and morphine in the rat formalin test | |
| WO2009007110A2 (en) | Combination of benzyl-4,5-dihydro-1h-imidazole derivative and an opiod recptor ligand | |
| WO1990000390A1 (en) | New synergistic preparations containing dezocine and a local anaesthetic and a new method of alleviation of pain | |
| Yoon et al. | Evaluation of interaction between intrathecal adenosine and MK801 or NBQX in a rat formalin pain model | |
| EP1702627A1 (en) | Analgesic combination of sodium channel blockers with opioid antagonists | |
| Vadivelu et al. | Buprenorphine pharmacology and clinical applications | |
| WO2021087268A1 (en) | Novel selective kappa opioid receptor antagonists and methods related thereto for treatment of addiction and neuropathic pain | |
| US20050187239A1 (en) | Synergistic l-methadone compositions and methods of use thereof | |
| WO2004096227A1 (en) | Pharmaceutical compositon comprising a cathepsin s inhibitor and an opioid | |
| MXPA01000447A (es) | Composicion topica que comprende un analgesico opioide y un antagonista de n-metil-d-aspartato | |
| KR20100126441A (ko) | 칸나비노이드 수용체 결합 화합물 및 아편유사제를 포함하는 조합물 | |
| KR20150108706A (ko) | 오피오이드 진통제 및 p7c3를 포함하는 진통제 조성물 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20050520 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20050520 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20080804 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20090113 |