Methopholine

Methopholine

Systematic (IUPAC) name
1-[2-(4-chlorophenyl)ethyl]-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline
Clinical data
Pregnancy cat.	?
Legal status	Legal
Identifiers
CAS number	2154-02-1 63937-57-5 (4'-nitromethopholine)
ATC code	None
PubChem	CID 16538
ChemSpider	15678 Y
UNII	72L4ZT2W1P Y
KEGG	D04986 Y
Chemical data
Formula	C20H24ClNO2
Mol. mass	345.87 g/mol
SMILES	eMolecules & PubChem
InChI InChI=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 Y Key:YBCPYHQFUMNOJG-UHFFFAOYSA-N Y
Y(what is this?)  (verify)

Methopholine is an opioid analgesic drug discovered in the 1950s by a team of Swiss researchers at Hoffmann-La Roche^[1].

Methopholine is an isoquinoline derivative which is not structurally related to most other opioids.^[2] It has around the same efficacy as an analgesic as codeine, and was evaluated for the treatment of postoperative pain.^[3][4][5] Methopholine tablets were marketed in the United States under the brand name of Versidyne, but the drug was withdrawn from the market in 1965 due to the occurrence of ophthalmic side-effects and the discovery that it could produce corneal opacities in dogs.^[6]

Methopholine has two enantiomers, 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 Analogues where the 4'-chloro group has been replaced by other groups have also been tested, the fluoro derivative being slightly more potent than chloro, and the nitro derivative being most potent of all, with the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.^[7][8]

4'-Nitromethopholine

References

1. ^ US Patent 3067203 - Tetrahydroisoquinoline Derivatives
2. ^ 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.
3. ^ 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.
4. ^ Cass LJ, Frederik WS. Methopholine, A New Analgesic Agent. American Journal of Medical Sciences. 1963 Nov;246:550-7.
5. ^ Sciorelli G. Plasma levels and renal excretion of unchanged methopholine in man. Experientia. 1967 Nov 15;23(11):934-6.
6. ^ Federal Register, March 27, 1965 (30 FR 4083).
7. ^ Casy AF, Parfitt RY. Opioid analgesics, chemistry and receptors. 1986, Plenum Press, New York. p 390. ISBN 0306421305
8. ^ Walter M, Besendorf H, Schnider O. Synthesen in der Isochinolinreihe Substituierte 1-[ω-(Nitrophenyl)alkyl]-1,2,3,4-tetrahydro-isochinoline. Helvetica Chimica Acta. 1963;46(4):1127-1131.