102320-84-3Relevant academic research and scientific papers
Antinociceptive potency ratios for (+)- and (-)-4-dimethylamino-2,2-diphenylpentanoate (the ethyl ester analogue of methadone)
Casy,Hassan,Rostron
, p. 249 - 250 (1979)
Early in the post-war investigations of acyclic analgesics of the 3,3-diphenylpropylamine class the unexpected discovery was made that the more active antipodal form of the ethyl ester analogue of methadone (Ia) was formed from the nitrile precursor (Ic) of the less active (+)-isomer of metahdone (Ib) (Pohland et al I.Me2NCHMeCH2CPh2R (a) R = CO2Et (b) R = COEt (c) R = CN (d) R = CHO (e) R = CH2OH 1949). Data gathered over the past ten years are now reported which confirm potency rankings of (+)-, (-)-, and (±)-forms of 'methadone ester', give evidence of the morphine-like pharmacological classification of the dextro isomer, and remove doubts about the configurational relationships of antipodal forms of methadone and its ethyl ester analogue. Original and novel pharmacological data are summarized. The isomeric potency ratios are of modest order (3-5:1) but consistently show the (+)-isomer to be the more active antipode with a potentency close to that of pethidine. In rats the (+)-ester (20 mg kg-1, i.v.) produced the typical morphine-like syndrome of lead pipe rigidity, reduced reaction to noxious stimuli, and respiratory depression, while in mice that same compound resulted in hot-plate activity, mydriasis, the Staub tail phenomenon and excitation - all effects were antagonized by nalorphine.
