The functional consequences of inhibition of monoamine oxidase type B: comparison of the pharmacological properties of L-deprenyl and MDL 72145.
The pharmacological properties of two selective inhibitors of monoamine oxidase (MAO) type B, L-deprenyl and MDL 72145 [(E)-2-(3,4-dimethoxyphenyl)-3-fluoroallylamine, HCl], have been investigated in rats and mice in relation to their effects on MAO. Selective inhibition of MAO B achieved following 18 h pretreatment with L-deprenyl and/or MDL 72145 did not per se lead to prominent pharmacological activity; no effects were seen in the mouse "Behavioural Despair" test, hypothermia induced by reserpine in mice was neither prevented nor reversed and there was no change in the cardiovascular responsiveness of the pithed rat to tyramine, noradrenaline or stimulation of the spinal sympathetic outflow. L-Deprenyl differed from MDL 72145 in that short term treatment with this drug caused positive effects in the "Behavioural Despair" test, reversal of reserpine hypothermia, indirect sympathomimetic stimulation of blood pressure and heart rate in the pithed rat and ipsilateral rotation in rats with unilateral nigro-striatal lesions. Qualitatively similar effects were seen with dexamphetamine. The marked difference between the pharmacological effects of MDL 72145 and L-deprenyl despite equivalent inhibition of MAO B suggests that many of the pharmacological actions of L-deprenyl result from its amphetamine-like sympathomimetic properties. MDL 72145 can, therefore, be considered a more reliable tool with which to explore the functional importance of MAO B inhibition in experimental animals and man.
D000499:Allylamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000588:Amines / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000201:enzymology; D004558:Electric Stimulation; D006439:Hemodynamics / Q000187:drug effects; D006892:Hydroxydopamines; D008297:Male; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000145:classification / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D016627:Oxidopamine; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000037:antagonists & inhibitors; D012642:Selegiline / Q000494:pharmacology*; D013116:Spinal Cord / Q000502:physiology; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000187:drug effects; D014439:Tyramine / Q000494:pharmacology
D000588:Amines; D006892:Hydroxydopamines; D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D012642:Selegiline; D000499:Allylamine; C040051:2-(3,4-dimethoxyphenyl)-3-fluoroallylamine; D012110:Reserpine; D016627:Oxidopamine; D009638:Norepinephrine; D014439:Tyramine