[Effect of a new antiparkinsonian drug himantane on monoamine oxidase activity].
N-2(adamantyl)hexamethyleneimine hydrochloride (hemantane) is a new potential antiparkinsonian drug targeted at several neurochemical systems. The drug exhibits the properties of a low-affinity noncompetitive blocker of the ion channels of glutamate NMDA receptors. Hemantane increases the content of dopamine in the striatum, while decreasing the level of dopamine metabolite dioxyphenylacetic acid (DOPAC). Investigation of the drug interaction with monoamine oxidases (MAOs) of the A and B types in vitro showed that hemantane acts as a weak competitive inhibitor of MAO-B (Ki = 470 +/- 70 microM) and partly protected MAO-B from irreversible inhibition by selegiline (deprenyl), while virtually not influencing the activity of MAO-A. Administered to C57BL6 mice (20-100 mg/kg), hemantane did not influence the activity of MAO-B measured in isolated cerebral mitochondria. At the same time, hemantane administered in combination with deprenyl significantly reduced activity of the latter drug and caused pronounced irreversible inhibition of mitochondrial MAO-B (comparable with the effect of deprenyl introduced alone). Therefore, inhibition of MAO-B may contribute to the spectrum of neurochemical activity of hemantane.
Val'dman
E A
EA
Laboratory of Psychopharmacology, Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiiskaya ul. 8, Moscow, 125315 Russia.
Voronina
T A
TA
Aksenova
L N
LN
Buneeva
O A
OA
Medvedev
A E
AE
D000218:Adamantane / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D012642:Selegiline / Q000378:metabolism / Q000494:pharmacology
D000978:Antiparkinson Agents; D008996:Monoamine Oxidase Inhibitors; C122112:N-(2-adamantyl)hexamethylenimine; D012642:Selegiline; D008995:Monoamine Oxidase; D000218:Adamantane