title: (-)Deprenyl and (-)1-phenyl-2-propylaminopentane, [(-)PPAP], act primarily as potent stimulants of action potential-transmitter release coupling in the catecholaminergic neurons.
abstract: The activity of the catecholaminergic neurons in the rat brain is enhanced significantly 30 min after the subcutaneous injection of very small doses of (-)deprenyl (threshold doses: 0.01 mg/kg for noradrenergic neurons and 0.025 mg/kg for dopaminergic neurons). As a catecholaminergic activity enhancer (CAE) substance (-)deprenyl is about ten times more potent than its parent compound, (-)methamphetamine. While the (+)methamphetamine is 3-5 times more potent than (-)methamphetammine in releasing catecholamines, the (-)methamphetamine is the more potent CAE substance. The mechanism of the CAE effect of (-)deprenyl and (-)PPAP, a deprenyl-derived substance devoid of MAO inhibitory potency, was studied in rats by measuring: a) the release of catecholamines from striatum, substantia nigra, tuberculum olfactorium and locus coeruleus; b) the stimulation induced release of 3H-noradrenaline from the isolated brain stem; and c) the antagonistic effect against tetrabenazine-induced depression of learning in the shuttle box. The CAE effect was found to be unrelated: a) to the inhibition of MAO activity; b) to the inhibition of presynaptic catecholamine receptors; c) to the inhibition of the uptake of catecholamines; and d) to the release of catecholamines. It was concluded that (-)deprenyl and (-)PPAP act primarily as potent stimulants of action potential-transmitter release coupling in the catecholaminergic neurons of the brain. We show that both (-)deprenyl and (-)PPAP enhance the inward Ca2+ current in sino-auricular fibers of the frog heart. (-)PPAP was much more potent than either (+)PPAP or (-)deprenyl in this test.
authors.affiliation: Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Knoll
authors.forename: I
authors.initials: I
authors.lastname: Miklya
authors.forename: B
authors.initials: B
authors.lastname: Knoll
authors.forename: R
authors.initials: R
authors.lastname: Markó
authors.forename: K
authors.initials: K
authors.lastname: Kelemen
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D002395:Catecholamines / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D011437:Propylamines / Q000494:pharmacology*; D011893:Rana esculenta; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014316:Tritium
chemical_list: D002395:Catecholamines; D018377:Neurotransmitter Agents; D011437:Propylamines; D014316:Tritium; C068473:N-(3-phenyl-n-propyl)-1-phenyl-2-aminopropane; D012642:Selegiline; D009638:Norepinephrine