hemantane and Disease-Models--Animal

Activity of hemantane, an amino adamantane derivative, exhibiting the properties of lowaffinity non-competitive NMDA receptor antagonist, was evaluated in experimental in vivo models of alcoholism. Hemantane had no effects on the formation and manifestation of behavioral sensitization to ethanol in DBA/2 mice. Under conditions of free choice between 10% ethanol and water, hemantane (20 mg/kg/day for 14 days, intraperitoneally) significantly reduced the daily ethanol intake in random-bred male rats with formed alcohol motivation (>4 g/kg of ethanol). During modelling of withdrawal syndrome, hemantane administered intraperitoneally in doses of 5-20 mg/kg dose-dependently attenuated alcohol-deprivation effect after acute withdrawal with no effects on protracted abstinence. It was found that hemantane suppressed alcohol drinking behavior in long-term ethanol experienced rats and attenuated alcohol-seeking behavior after acute withdrawal.

Topics: Adamantane; Alcoholism; Animals; Animals, Outbred Strains; Choice Behavior; Disease Models, Animal; Male; Mice; Mice, Inbred DBA; Motivation; Rats; Receptors, N-Methyl-D-Aspartate; Substance Withdrawal Syndrome

The effects of anti-parkinsonian drug hemantane [(2-adamantyl)hexamethylenimine] (10 mg/kg, p. o.) and/or antibiotic drug doxycycline (100 mg/kg, p. o.), as well as that of neurotoxin 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP) (4 x 20 mg/kg, i. p.) were studied in elevated plus maze test on C57BL/6 mice. On second day after injection, MPTP decreased the locomot or activity in comparison to saline. Acute administration of hemantane or doxycycline failed to influence locomotion in mice, while their combination normalized motor activity. The results obtained confirm the role of inflammatory processes in parkinsonism and suggest expediency of combined pharmacotherapy of neurodegenerative diseases.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Adamantane; Animals; Antiparkinson Agents; Disease Models, Animal; Doxycycline; Drug Combinations; Drug Synergism; Male; Maze Learning; Mice; Mice, Inbred C57BL; Motor Activity; Neurotoxins; Parkinson Disease, Secondary

Chronic administration of levodopa and benserazide (10 and 15 mg/kg, respectively) cause the development of dyskinesia in rats with model parkinsonian syndrome induced by injection of 6-hydroxydopamine in left substantia nigra. The chronic administration of these drugs together with amantadine (20 mg/kg) accelerates the onset of latency and increases the magnitude of dyskinesia. Chronic administration of levodopa and benserazide together with hemantane (10 mg/kg) slows down the development and decreases the magnitude of levodopa-induced abnormal involuntary movements as measured for limb, orolingual and rotatory movements.

Topics: Adamantane; Amantadine; Animals; Behavior, Animal; Benserazide; Disease Models, Animal; Dyskinesia, Drug-Induced; Levodopa; Male; Oxidopamine; Parkinsonian Disorders; Rats; Substantia Nigra

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