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{{Short description|Chemical compound}} |
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{{Drugbox |
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{{Drugbox |
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| verifiedrevid = 444012148 |
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| verifiedrevid = 450690409 |
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| IUPAC_name = 1--6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline |
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| IUPAC_name = 1--6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline |
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| image = Methopholine.svg |
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| image = Methopholine.svg |
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| width = 180 |
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| width = 180 |
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| legal_UK = |
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| legal_UK = |
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| legal_US = |
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| legal_US = |
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| legal_status = Legal |
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| legal_status = ? |
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| routes_of_administration = |
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| routes_of_administration = |
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<!--Pharmacokinetic data--> |
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<!--Pharmacokinetic data--> |
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| metabolism = |
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| metabolism = |
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| elimination_half-life = |
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| elimination_half-life = |
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| excretion = |
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| excretion = |
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<!--Identifiers--> |
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<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 2154-02-1 |
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| CAS_number = 2154-02-1 |
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| CAS_supplemental = <br /> 63937-57-5 (4'-nitromethopholine) |
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| CAS_supplemental = <br /> 63937-57-5 (4'-nitromethopholine) |
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<!--Chemical data--> |
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<!--Chemical data--> |
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| C=20 | H=24 | Cl=1 | N=1 | O=2 |
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| C=20 | H=24 | Cl=1 | N=1 | O=2 |
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| smiles = ClC1=CC=C(CCC2C3=CC(OC)=C(OC)C=C3CCN2C)C=C1 |
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| molecular_weight = 345.87 g/mol |
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| smiles = Clc1ccc(cc1)CCC3c2c(cc(OC)c(OC)c2)CCN3C |
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| InChI = 1/C20H24ClNO2/c1-22-11-10-15-12-19(23-2)20(24-3)13-17(15)18(22)9-6-14-4-7-16(21)8-5-14/h4-5,7-8,12-13,18H,6,9-11H2,1-3H3 |
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| InChIKey = YBCPYHQFUMNOJG-UHFFFAOYAD |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C20H24ClNO2/c1-22-11-10-15-12-19(23-2)20(24-3)13-17(15)18(22)9-6-14-4-7-16(21)8-5-14/h4-5,7-8,12-13,18H,6,9-11H2,1-3H3 |
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| StdInChI = 1S/C20H24ClNO2/c1-22-11-10-15-12-19(23-2)20(24-3)13-17(15)18(22)9-6-14-4-7-16(21)8-5-14/h4-5,7-8,12-13,18H,6,9-11H2,1-3H3 |
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'''Methopholine''' is an ] ] drug discovered in the 1950s by a team of Swiss researchers at Hoffmann-La Roche<ref>US Patent 3067203 - Tetrahydroisoquinoline Derivatives</ref>. |
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'''Metofoline''' (]), also known as '''methofoline''' (]), is an ] ] drug discovered in the 1950s by a team of Swiss researchers at Hoffmann-La Roche.<ref>{{ cite patent | country = US | status = patent | number = 3067203 | title = Tetrahydroisoquinoline Derivatives | assign1 = Hoffmann-La Roche | gdate = 1962-12-04 }}</ref> |
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Methopholine is an ] derivative which is not structurally related to most other opioids.<ref>Feinberg AP, Creese I, Snyder SH. The opiate receptor: a model explaining structure-activity relationships of opiate agonists and antagonists. ''Proceedings of the National Academy of Sciences U S A''. 1976 Nov;73(11):4215-9.</ref> It has around the same efficacy as an analgesic as ], and was evaluated for the treatment of postoperative pain.<ref>Moore J, Foldes FF, Davidson GM. An evaluation of the efficacy of methopholine for the relief of postoperative pain. ''American Journal of Medical Sciences''. 1962 Sep;244:337-43.</ref><ref>Cass LJ, Frederik WS. Methopholine, A New Analgesic Agent. ''American Journal of Medical Sciences''. 1963 Nov;246:550-7.</ref><ref>Sciorelli G. Plasma levels and renal excretion of unchanged methopholine in man. ''Experientia''. 1967 Nov 15;23(11):934-6.</ref> Methopholine tablets were marketed in the United States under the brand name of Versidyne, but the drug was withdrawn from the market in 1965 due to the occurrence of ] side-effects and the discovery that it could produce corneal opacities in dogs.<ref>''Federal Register'', March 27, 1965 (30 FR 4083).</ref> |
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Methopholine is an ] derivative which is not structurally related to most other opioids.<ref>{{cite journal | vauthors = Feinberg AP, Creese I, Snyder SH | title = The opiate receptor: a model explaining structure-activity relationships of opiate agonists and antagonists | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 73 | issue = 11 | pages = 4215–9 | date = November 1976 | pmid = 186791 | pmc = 431391 | doi = 10.1073/pnas.73.11.4215 | bibcode = 1976PNAS...73.4215F | doi-access = free }}</ref> |
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However, its structural similarity to the non-opioid alkaloid ] is notable. |
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Metofoline has around the same efficacy as an analgesic as ], and was evaluated for the treatment of postoperative pain.<ref>{{cite journal | vauthors = Moore J, Foldes FF, Davidson GM | title = An evaluation of the efficacy of methopholine for the relief of postoperative pain | journal = The American Journal of the Medical Sciences | volume = 244 | pages = 337–43 | date = September 1962 | issue = 3 | pmid = 14475666 | doi = 10.1097/00000441-196209000-00010 | s2cid = 36562481 }}</ref><ref>{{cite journal | vauthors = Cass LJ, Frederik WS | title = Methopholine, A New Analgesic Agent | journal = The American Journal of the Medical Sciences | volume = 246 | pages = 550–7 | date = November 1963 | issue = 5 | pmid = 14082642 | doi = 10.1097/00000441-196311000-00005 }}</ref><ref>{{cite journal | vauthors = Sciorelli G | title = Plasma levels and renal excretion of unchanged methopholine in man | journal = Experientia | volume = 23 | issue = 11 | pages = 934–6 | date = November 1967 | pmid = 6057015 | doi = 10.1007/bf02136231 | s2cid = 32258639 }}</ref> Metofoline tablets were marketed in the United States under the brand name of Versidyne,<ref>{{cite journal | vauthors = Ryan RE | title = Versidyne. Its use in vascular headache | journal = Headache | volume = 2 | pages = 203–8 | date = January 1963 | issue = 4 | pmid = 13975764 | doi = 10.1111/j.1526-4610.1963.hed0204203.x | s2cid = 2891222 }}</ref> but the drug was withdrawn from the market in 1965 due to the occurrence of ] side-effects alongside the discovery that the drug could produce ] in dogs.<ref>{{Federal Register|30|4083}} March 27, 1965</ref> |
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Metofoline has two ]s, with the ''levo'' (R) enantiomer being the active form, around 3x the potency of codeine, and the (S) enantiomer being inactive. |
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Methopholine has two ]s, with the ''levo'' (R) enantiomer being the active form, around 3x the potency of codeine, and the (S) enantiomer being inactive. Analogues where the 4'-chloro group has been replaced by other groups have also been tested, the fluoro derivative being slightly more potent than chloro, and the nitro derivative being most potent of all, with the racemic 4'-nitromethopholine being around 20x the potency of codeine.<ref>Casy AF, Parfitt RY. Opioid analgesics, chemistry and receptors. 1986, Plenum Press, New York. p 390. ISBN 0306421305</ref><ref>Walter M, Besendorf H, Schnider O. Synthesen in der Isochinolinreihe Substituierte 1--1,2,3,4-tetrahydro-isochinoline. ''Helvetica Chimica Acta''. 1963;46(4):1127-1131.</ref> |
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] where the 4'-chloro group has been replaced by other ]s have also been tested, the fluoro derivative being slightly more potent than chloro, and the nitro derivative being most potent of all, with the racemic 4'-nitromethopholine being around 20x the potency of codeine.<ref>{{ cite book | vauthors = Casy AF, Parfitt RY | title = Opioid Analgesics, Chemistry and Receptors | year = 1986 | publisher = Plenum Press | location = New York | page = 390 | isbn = 0-306-42130-5 }}</ref><ref>{{Cite journal | vauthors = Walter M, Besendorf H, Schnider O | doi = 10.1002/hlca.19630460405 | title = Synthesen in der Isochinolinreihe. Substituierte 1--1,2,3,4-tetrahydro-isochinoline | journal = Helvetica Chimica Acta | volume = 46 | issue = 4 | pages = 1127–1132 | year = 1963 }}</ref> |
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Later research was carried out by Bristol-Myer in the 1960s<ref>US Patent 3378561A 1-beta-arylthioethyltetrahydro-isoquinolines</ref> and animal studies suggested derivatives with significantly increased analgesic activity of over x50 codeine.<ref>'Tetrahydroisoquinolines. I. The Preparation and Analgesic Activity of Some 1-Thiophenoxyethyltetrahydroisoquinolines and 1-Phenoxyethyltetrahydroisoquinolines'J. Med. Chem. 1969 Jul;12(4):575-80. doi: 10.1021/jm00304a003.</ref> |
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== See also == |
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* ] |
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* ] |
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== References == |
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== References == |
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{{Reflist|30em}} |
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{{Opioidergics}} |
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