Pharmacological comparison between the actions of methamphetamine and 1-aminoindan stereoisomers on sympathetic nervous function in rat vas deferens.
The selective monoamine oxidase-B inhibitor selegiline (deprenyl) causes sympathomimetic effects and is metabolised to R(-)-methamphetamine and R(-)-amphetamine. The new monoamine oxidase-B inhibitor rasagiline is devoid of sympathomimetic effects and is metabolised to R(+)-1-aminoindan. Sympathomimetic effects of methamphetamine and 1-aminoindan enantiomers were compared in the rat vas deferens. R(-)-methamphetamine and S(+)-methamphetamine caused initial potentiation and subsequent inhibition of the field stimulation-induced twitch response of isolated rat vas deferens (0.1 Hz). EC(50) values for inhibition of twitch in prazosin-treated vas deferens were 0.36+/-0.13 and 1.64+/-0.10 microM (mean+/-S.E.M.) for S(+)- and R(-)-methamphetamine, respectively. There was no difference between S(+)-methamphetamine and R(-)-methamphetamine in potentiation of postsynaptic contractile response to noradrenaline. R(+)- and S(-)-1-aminoindan increased twitch response only at concentrations above 30 microM. R(-)-methamphetamine has similar potency to S(+)-methamphetamine in potentiation of noradrenaline-mediated responses and can therefore play a role in the sympathomimetic effects of selegiline.
Glezer
Sofia
S
Department of Pharmacology, Faculty of Medicine, Technion, P.O. Box 9649, Bat-Galim, Haifa 31096, Israel.
Finberg
John P M
JP
D000320:Adrenergic Fibers / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007189:Indans / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014649:Vas Deferens / Q000187:drug effects* / Q000294:innervation / Q000502:physiology
D007189:Indans; C016992:1-aminoindan; D008694:Methamphetamine