JP4287660B2 - 疼痛の予防療法用薬物の調製のためのアセチルｌ−カルニチンの使用 - Google Patents
疼痛の予防療法用薬物の調製のためのアセチルｌ−カルニチンの使用 Download PDFInfo
- Publication number
- JP4287660B2 JP4287660B2 JP2002592919A JP2002592919A JP4287660B2 JP 4287660 B2 JP4287660 B2 JP 4287660B2 JP 2002592919 A JP2002592919 A JP 2002592919A JP 2002592919 A JP2002592919 A JP 2002592919A JP 4287660 B2 JP4287660 B2 JP 4287660B2
- Authority
- JP
- Japan
- Prior art keywords
- carnitine
- acetyl
- acid
- pain
- days
- 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.)
- Expired - Fee Related
Links
- RDHQFKQIGNGIED-MRVPVSSYSA-N O-acetyl-L-carnitine Chemical compound CC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C RDHQFKQIGNGIED-MRVPVSSYSA-N 0.000 title claims abstract description 52
- 238000011321 prophylaxis Methods 0.000 title claims description 6
- 239000003814 drug Substances 0.000 title abstract description 17
- 208000002193 Pain Diseases 0.000 title abstract description 16
- 230000036407 pain Effects 0.000 title abstract description 16
- 238000002360 preparation method Methods 0.000 title abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 239000002253 acid Substances 0.000 claims description 21
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 8
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 5
- 229940095064 tartrate Drugs 0.000 claims description 5
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
- 208000004550 Postoperative Pain Diseases 0.000 claims description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 4
- -1 mucate Substances 0.000 claims description 4
- CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 claims description 3
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 claims description 3
- NDVRKEKNSBMTAX-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;phosphoric acid Chemical compound OP(O)(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O NDVRKEKNSBMTAX-BTVCFUMJSA-N 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- 229940009098 aspartate Drugs 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- 239000011777 magnesium Substances 0.000 claims description 2
- 229940095060 magnesium tartrate Drugs 0.000 claims description 2
- MUZDLCBWNVUYIR-ZVGUSBNCSA-L magnesium;(2r,3r)-2,3-dihydroxybutanedioate Chemical compound [Mg+2].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O MUZDLCBWNVUYIR-ZVGUSBNCSA-L 0.000 claims description 2
- QUIOHQITLKCGNW-TYYBGVCCSA-L magnesium;(e)-but-2-enedioate Chemical compound [Mg+2].[O-]C(=O)\C=C\C([O-])=O QUIOHQITLKCGNW-TYYBGVCCSA-L 0.000 claims description 2
- PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 229940066528 trichloroacetate Drugs 0.000 claims description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims description 2
- PLSARIKBYIPYPF-UHFFFAOYSA-H trimagnesium dicitrate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O PLSARIKBYIPYPF-UHFFFAOYSA-H 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- QWJSAWXRUVVRLH-LREBCSMRSA-M 2-hydroxyethyl(trimethyl)azanium;(2r,3r)-2,3,4-trihydroxy-4-oxobutanoate Chemical compound C[N+](C)(C)CCO.OC(=O)[C@H](O)[C@@H](O)C([O-])=O QWJSAWXRUVVRLH-LREBCSMRSA-M 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 1
- 150000001805 chlorine compounds Chemical group 0.000 claims 1
- 229960005336 magnesium citrate Drugs 0.000 claims 1
- 235000002538 magnesium citrate Nutrition 0.000 claims 1
- 239000004337 magnesium citrate Substances 0.000 claims 1
- 229940091250 magnesium supplement Drugs 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 12
- 238000009117 preventive therapy Methods 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 31
- 241000699670 Mus sp. Species 0.000 description 24
- 238000007920 subcutaneous administration Methods 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 241001465754 Metazoa Species 0.000 description 21
- 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 20
- 230000000202 analgesic effect Effects 0.000 description 16
- 230000036592 analgesia Effects 0.000 description 15
- 230000000694 effects Effects 0.000 description 11
- 229960005181 morphine Drugs 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 208000000114 Pain Threshold Diseases 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 230000037040 pain threshold Effects 0.000 description 9
- 230000000069 prophylactic effect Effects 0.000 description 9
- 238000011282 treatment Methods 0.000 description 9
- 208000004454 Hyperalgesia Diseases 0.000 description 8
- 208000035154 Hyperesthesia Diseases 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 230000003502 anti-nociceptive effect Effects 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 230000003187 abdominal effect Effects 0.000 description 6
- 230000008602 contraction Effects 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 4
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 4
- 206010048010 Withdrawal syndrome Diseases 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 229950006874 kainic acid Drugs 0.000 description 4
- HOKKHZGPKSLGJE-UHFFFAOYSA-N N-methyl-D-aspartic acid Natural products CNC(C(O)=O)CC(O)=O HOKKHZGPKSLGJE-UHFFFAOYSA-N 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- VLSMHEGGTFMBBZ-UHFFFAOYSA-N alpha-Kainic acid Natural products CC(=C)C1CNC(C(O)=O)C1CC(O)=O VLSMHEGGTFMBBZ-UHFFFAOYSA-N 0.000 description 3
- 229940035676 analgesics Drugs 0.000 description 3
- 239000000730 antalgic agent Substances 0.000 description 3
- VLSMHEGGTFMBBZ-OOZYFLPDSA-N kainic acid Chemical compound CC(=C)[C@H]1CN[C@H](C(O)=O)[C@H]1CC(O)=O VLSMHEGGTFMBBZ-OOZYFLPDSA-N 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000004973 motor coordination Effects 0.000 description 3
- 230000003040 nociceptive effect Effects 0.000 description 3
- 229960001412 pentobarbital Drugs 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 208000005156 Dehydration Diseases 0.000 description 2
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 238000007913 intrathecal administration Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000003149 muscarinic antagonist Substances 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-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
- KSXTUUUQYQYKCR-LQDDAWAPSA-M 2,3-bis[[(z)-octadec-9-enoyl]oxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCC(=O)OCC(C[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC KSXTUUUQYQYKCR-LQDDAWAPSA-M 0.000 description 1
- 239000003412 4 aminobutyric acid B receptor blocking agent Substances 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- KPYSYYIEGFHWSV-UHFFFAOYSA-N Baclofen Chemical compound OC(=O)CC(CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-UHFFFAOYSA-N 0.000 description 1
- 206010064012 Central pain syndrome Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 102000003676 Glucocorticoid Receptors Human genes 0.000 description 1
- 108090000079 Glucocorticoid Receptors Proteins 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- NHTGHBARYWONDQ-JTQLQIEISA-N L-α-methyl-Tyrosine Chemical compound OC(=O)[C@](N)(C)CC1=CC=C(O)C=C1 NHTGHBARYWONDQ-JTQLQIEISA-N 0.000 description 1
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 1
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 1
- 229940123247 Neurotransmitter antagonist Drugs 0.000 description 1
- PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 1
- GMZVRMREEHBGGF-UHFFFAOYSA-N Piracetam Chemical compound NC(=O)CN1CCCC1=O GMZVRMREEHBGGF-UHFFFAOYSA-N 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000003443 Unconsciousness Diseases 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 229940116352 animax Drugs 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 230000003070 anti-hyperalgesia Effects 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- 229960000794 baclofen Drugs 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229960004203 carnitine Drugs 0.000 description 1
- 230000000768 catecholaminergic effect Effects 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- QIIVUOWTHWIXFO-UHFFFAOYSA-N cgp-35348 Chemical compound CCOC(OCC)P(O)(=O)CCCN QIIVUOWTHWIXFO-UHFFFAOYSA-N 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 208000013088 frontal headache Diseases 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000003371 gabaergic effect Effects 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 230000037120 immobility Effects 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229960004127 naloxone Drugs 0.000 description 1
- 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 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 230000000508 neurotrophic effect Effects 0.000 description 1
- 230000036441 nociceptive stimulation Effects 0.000 description 1
- 239000003401 opiate antagonist Substances 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 208000027232 peripheral nervous system disease Diseases 0.000 description 1
- 229960001697 physostigmine Drugs 0.000 description 1
- PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 description 1
- 229960004526 piracetam Drugs 0.000 description 1
- RMHMFHUVIITRHF-UHFFFAOYSA-N pirenzepine Chemical compound C1CN(C)CCN1CC(=O)N1C2=NC=CC=C2NC(=O)C2=CC=CC=C21 RMHMFHUVIITRHF-UHFFFAOYSA-N 0.000 description 1
- 229960004633 pirenzepine Drugs 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 230000002295 serotoninergic effect Effects 0.000 description 1
- 230000004617 sleep duration Effects 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 230000008925 spontaneous activity Effects 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 210000002438 upper gastrointestinal tract Anatomy 0.000 description 1
Images
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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/221—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having an amino group, e.g. acetylcholine, acetylcarnitine
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Emergency Medicine (AREA)
- Rheumatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2001RM000293A ITRM20010293A1 (it) | 2001-05-29 | 2001-05-29 | Uso della acetil-l-carnetina per la preparazione di un medicamento per la prevenzione del dolore. |
| PCT/IT2002/000336 WO2002096409A1 (en) | 2001-05-29 | 2002-05-24 | Use of acetyl l-carnitine for the preparation of a medication for the preventive therapy for pain |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2004532865A JP2004532865A (ja) | 2004-10-28 |
| JP2004532865A5 JP2004532865A5 (enExample) | 2006-01-05 |
| JP4287660B2 true JP4287660B2 (ja) | 2009-07-01 |
Family
ID=11455557
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002592919A Expired - Fee Related JP4287660B2 (ja) | 2001-05-29 | 2002-05-24 | 疼痛の予防療法用薬物の調製のためのアセチルｌ−カルニチンの使用 |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US20040152781A1 (enExample) |
| EP (1) | EP1399141B1 (enExample) |
| JP (1) | JP4287660B2 (enExample) |
| KR (1) | KR100873748B1 (enExample) |
| AT (1) | ATE374021T1 (enExample) |
| CA (1) | CA2448242C (enExample) |
| CY (1) | CY1107037T1 (enExample) |
| CZ (1) | CZ20033220A3 (enExample) |
| DE (1) | DE60222662T2 (enExample) |
| DK (1) | DK1399141T3 (enExample) |
| ES (1) | ES2290292T3 (enExample) |
| HU (1) | HUP0401294A3 (enExample) |
| IT (1) | ITRM20010293A1 (enExample) |
| MX (1) | MXPA03010919A (enExample) |
| PL (1) | PL367616A1 (enExample) |
| PT (1) | PT1399141E (enExample) |
| SK (1) | SK287559B6 (enExample) |
| WO (1) | WO2002096409A1 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ITRM20040606A1 (it) * | 2004-12-13 | 2005-03-13 | Sigma Tau Ind Farmaceuti | Uso della acetil l-carnitina per il trattamento della sindrome fibromialgica. |
| JP5685362B2 (ja) * | 2005-04-26 | 2015-03-18 | シグマ−タウ・インドゥストリエ・ファルマチェウチケ・リウニテ・ソシエタ・ペル・アチオニＳｉｇｍａ−Ｔａｕ Ｉｎｄｕｓｔｒｉｅ Ｆａｒｍａｃｅｕｔｉｃｈｅ Ｒｉｕｎｉｔｅ Ｓｏｃｉｅｔａ Ｐｅｒ Ａｚｉｏｎｉ | 有痛性末梢糖尿病性神経障害の予防のためのアセチルｌ−カルニチン |
| IT202200022437A1 (it) | 2022-11-02 | 2024-05-02 | Chiesi Italia S P A | Composizione farmaceutica comprendente l-acetilcarnitina e beta-cariofillene |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0150688B1 (en) * | 1983-12-28 | 1987-04-22 | Sigma-Tau Industrie Farmaceutiche Riunite S.p.A. | Salts of l-carnitine and alkanoyl l-carnitines and process for preparing same |
| IT1196564B (it) * | 1986-08-04 | 1988-11-16 | Sigma Tau Ind Farmaceuti | Impiego di acetil l-carnitina nel trattamento terapeutico delle neuropatie periferiche |
| IT1277147B1 (it) * | 1995-01-20 | 1997-11-04 | Sigma Tau Ind Farmaceuti | Uso della carnitina e i suoi derivati per ridurre gli effetti tossici della ciclosporina-a e di altri farmaci immunosoppressivi. |
-
2001
- 2001-05-29 IT IT2001RM000293A patent/ITRM20010293A1/it unknown
-
2002
- 2002-05-24 HU HU0401294A patent/HUP0401294A3/hu unknown
- 2002-05-24 US US10/478,379 patent/US20040152781A1/en not_active Abandoned
- 2002-05-24 MX MXPA03010919A patent/MXPA03010919A/es active IP Right Grant
- 2002-05-24 KR KR1020037015574A patent/KR100873748B1/ko not_active Expired - Fee Related
- 2002-05-24 EP EP02728055A patent/EP1399141B1/en not_active Expired - Lifetime
- 2002-05-24 AT AT02728055T patent/ATE374021T1/de not_active IP Right Cessation
- 2002-05-24 PT PT02728055T patent/PT1399141E/pt unknown
- 2002-05-24 JP JP2002592919A patent/JP4287660B2/ja not_active Expired - Fee Related
- 2002-05-24 CA CA2448242A patent/CA2448242C/en not_active Expired - Fee Related
- 2002-05-24 DE DE60222662T patent/DE60222662T2/de not_active Expired - Lifetime
- 2002-05-24 DK DK02728055T patent/DK1399141T3/da active
- 2002-05-24 CZ CZ20033220A patent/CZ20033220A3/cs unknown
- 2002-05-24 SK SK1584-2003A patent/SK287559B6/sk not_active IP Right Cessation
- 2002-05-24 ES ES02728055T patent/ES2290292T3/es not_active Expired - Lifetime
- 2002-05-24 WO PCT/IT2002/000336 patent/WO2002096409A1/en not_active Ceased
- 2002-05-24 PL PL02367616A patent/PL367616A1/xx not_active IP Right Cessation
-
2007
- 2007-11-28 CY CY20071101520T patent/CY1107037T1/el unknown
-
2008
- 2008-09-26 US US12/232,945 patent/US20090062388A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| DK1399141T3 (da) | 2008-01-02 |
| SK15842003A3 (sk) | 2004-06-08 |
| DE60222662T2 (de) | 2008-06-26 |
| CY1107037T1 (el) | 2012-09-26 |
| PT1399141E (pt) | 2007-11-16 |
| HUP0401294A2 (hu) | 2004-12-28 |
| ITRM20010293A1 (it) | 2002-11-29 |
| EP1399141A1 (en) | 2004-03-24 |
| WO2002096409A1 (en) | 2002-12-05 |
| CA2448242C (en) | 2011-01-11 |
| PL367616A1 (en) | 2005-03-07 |
| DE60222662D1 (de) | 2007-11-08 |
| JP2004532865A (ja) | 2004-10-28 |
| ES2290292T3 (es) | 2008-02-16 |
| SK287559B6 (sk) | 2011-02-04 |
| KR100873748B1 (ko) | 2008-12-12 |
| ITRM20010293A0 (it) | 2001-05-29 |
| CA2448242A1 (en) | 2002-12-05 |
| HUP0401294A3 (en) | 2008-04-28 |
| CZ20033220A3 (en) | 2004-06-16 |
| ATE374021T1 (de) | 2007-10-15 |
| US20040152781A1 (en) | 2004-08-05 |
| KR20040003030A (ko) | 2004-01-07 |
| US20090062388A1 (en) | 2009-03-05 |
| MXPA03010919A (es) | 2004-02-27 |
| EP1399141B1 (en) | 2007-09-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4599342A (en) | Pharmaceutical products providing enhanced analgesia | |
| US6608088B1 (en) | Use of donerezil for the treatment of functional and/or organic pain syndromes | |
| EP1219624B1 (en) | Remedies for neuropathic pain and model animals of neuropathic pain | |
| US6326404B1 (en) | Use of O-desmethyl-N-mono-desmethyl-tramadol | |
| JP3559572B2 (ja) | 急性痛および慢性痛用鎮痛剤 | |
| JP4287660B2 (ja) | 疼痛の予防療法用薬物の調製のためのアセチルｌ−カルニチンの使用 | |
| US6713497B1 (en) | Use of vitamin B6 to mitigate visual field defects associated with the use of GABAergic drugs in mammals | |
| EP1007041A1 (en) | Composition for treating pain | |
| EP1610785B1 (en) | Pharmaceutical combination for the treatment of spasticity and/or pain | |
| WO1998046601A1 (en) | Composition for treating pain | |
| EP1244498B1 (en) | Combination of trimebutine with an opioid analgesic | |
| US20080287480A1 (en) | Therapeutic Combination Comprising a Nmda Receptors Blocker and a Narcotic Analgesic Substance | |
| WO2005044248A1 (en) | Use of proglumide and tramadol in the treatment of pain |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20050518 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20050518 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20081118 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090216 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20090317 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20090327 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120403 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| LAPS | Cancellation because of no payment of annual fees |