hemantane and Parkinson-Disease--Secondary

A single intraperitoneal injection of MPTP neurotoxin (30 mg/kg) in C57BL/6 mice causes desynchronization of EEG with a decrease of theta-1 activity and a growth of beta activity in the interval of 15-30 Hz. Subchronic administration of the new antiparkinsonian drug hemantane (injection form) in a dose of 10 mg/kg makes the power of MPTP-induced beta oscillations less pronounced and leads to its reliable decrease within 24 h. This effect of hemantane administration was manifested during the entire period of observations.

Topics: Adamantane; Animals; Beta Rhythm; Male; Mice; MPTP Poisoning; Parkinson Disease, Secondary; Theta Rhythm; Time Factors

Presymptomatic (premotor) stage of Parkinson's disease has been modeled in rats by intranigral bilateral injections of neurotoxin MPTP. Three weeks after surgery, rats demonstrated cognitive deficit and depressive-like behavior without definite motor impairment. Pretreatment with hemantane (10 mg/kg) and the reference drug amantadine (20 mg/kg) 5 days before MPTP and further administration during 3 weeks after MPTP preserve cognitive function and prevented depressive disturbances in rats. The antidepressive effect of hemantane was more pronounced than that of amantadine. Results obtained, together with data on hemantane mechanism of action, allow hemantane to be considered as a promising drug for the treatment of Parkinson's disease with potential to decrease the rate of disease progression when administered on early stages.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Adamantane; Amantadine; Animals; Antiparkinson Agents; Cognition; Drug Administration Schedule; Male; Neurotoxins; Parkinson Disease, Secondary; Rats; Time Factors

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

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