[Estimation of the protective effect of the novel potential antiparkinsonian agent himantane against MPTP neurotoxicity].
N-(Adamant-2-yl)hexamethyleneimine hydrochloride (hemantane) is a new potential antiparkinsonian drug with a complex mechanism of action. The drug exhibits the properties of a low-affinity blocker of the ion channels of NMDA receptors, increases the dopamine content in striatum, and inhibits monoamine oxidases (MAO-B). This combination of properties suggests that hemantane can also possess neuroprotector properties. In this context, the ability of hemantane to prevent from the development of MPTP neurotoxin action on the locomotor activity in mice and the EEG activity in rats has been studied. Preliminary single (and the more so, repeated over a period of 5 days) peroral administration of hemantane in a dose of 10 mg/kg significantly reduced the manifestations of MPTP-induced oligokinesia in C57BL/6 mice. Acute of subchronic (7-day) pretreatment with hemantane prevented the development of EEG changes typical of parkinsonism. The results of statistical EEG data processing showed that a systemic introduction of MPTP (30 mg/kg) on the background of hemantane pretreatment produced no reliable changes against control characteristics. Thus, hemantane is capable of protecting experimental animals from MPTP neurotoxicity.
Val'dman
E A
EA
Laboratory of Psychopharmacology, Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiiskaya ul. 8, Moscow, 125315 Russia.
Nerobkova
L N
LN
Voronina
T A
TA
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000284:Administration, Oral; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats
D000978:Antiparkinson Agents; C122112:N-(2-adamantyl)hexamethylenimine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000218:Adamantane