hemantane and Parkinson-Disease

The pharmacokinetics ofhemantane after administration in different ways has been studied in rats. It is established that hemantane introduced both orally (p.o.) and intravenously (i.v.) is very intensively metabolized, with the main metabolites characterized by m/z = 250 and 266 and detected for 6 hours after the administration in both ways. Hemantane shows high rate of permeability into its target organ--brain--whereas the permeation of its metabolites is extremely low. The absolute bioavailability ofhemantane upon p.o. administration was 14.1%. The substance is subject to the "first-pass effect". The unchanged substance was determined in daily urine and feces in very small fractions of the administered dose: 0.23% in urine and 0.08% in feces after i.v. administration and 0.02% in feces after p.o. administration. Thus, it may be concluded that the substance is completely absorbed in rats from the gastro-intestinal tract into systemic blood circulation.

Topics: Adamantane; Animals; Antiparkinson Agents; Biological Availability; Biotransformation; Brain Chemistry; Chromatography, Liquid; Feces; Humans; Injections, Intraperitoneal; Injections, Intravenous; Male; Parkinson Disease; Rats; Rats, Inbred Strains; Tandem Mass Spectrometry; Tissue Distribution

The influence of the new antiparkinsonian drug hemantane on D1 receptors in striatum, 5-HT1A receptors in hippocampus, and 5-HT2A receptors in frontal cortex of intact and MPP+-treated (3 microg/0.6 ml dist., intranigral) rats was studied. Hemantane (20 mg/kg, i.p.) was administrated subchronically for 7 days (beginning a day after MPP+ injection). A modulatory effect of hemantane on D1, 5-HT1A and 5-HT2A receptors was revealed. It was found that hemantane increased the binding site density (Bmax) of D1 and 5-HT1A receptors and decreased the binding site density of 5-HT2A receptors without changing the affinity (Kd) to the selective ligands. These results demonstrate that subchronic administration of hemantane leads to the functional rearrangement of dopamine and serotonin receptors in the brain of both intact and MPP+-treated rats.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Adamantane; Animals; Corpus Striatum; Disease Models, Animal; Hippocampus; Male; MPTP Poisoning; Neurotoxins; Parkinson Disease; Parkinson Disease, Secondary; Rats; Receptor, Serotonin, 5-HT1A; Receptor, Serotonin, 5-HT2A; Receptors, Dopamine D1