hemantane and Parkinsonian-Disorders

Potential neuroprotective activity of the novel antiparkinsonian drug hemantane (hydrochloride N-2-(adamantyl)-hexamethylenimine) in comparison to amantadine has been studied in various regimes of administration on human neuroblastoma SH-SY5Y cell line injury induced by 6-hydroxydopamine (6-OHDA), which is used as in vitro model of dopaminergic neurons for Parkinson's disease. Two regimes of hemantane and amantadine administration in a range of final concentrations 10⁻⁶-10⁻⁸ M were used either prior to or immediately after 6-OHDA introduction. MTT colorimetric assay was used to assess the viability of test cells. Significant decrease in viability of SH-SY5Y cells treated with 6-OHDA was observed. The addition of hemantane to cell medium produced cytoprotective effects in both regimes of administration--before and after 6-OHDA--at concentrations 10⁻⁷ M and 10⁻⁶-10⁻⁸ M, respectively. Amantadine in con- centrations 10⁻⁷-10⁻⁸ M was effective to increase cell survival only when administered after 6-OHDA. These results show that hemantane has a greater neu-roprotective potential in comparison to amantadine.

Topics: Adamantane; Amantadine; Cell Line, Tumor; Cytoprotection; Dose-Response Relationship, Drug; Humans; Models, Biological; Neuroblastoma; Parkinsonian Disorders

Levodopa-induced heavy dyskinesia was modeled in rats with severe hemiparkinsonian syndrome induced by injection of 6-hydroxydopamine in the left medial forebrain bundle. It is established that the antidyskinetic effect of the injectable dosage form of a new antiparkinsonian drug hemantane (5 mg/kg) after a single intravenous administration is weaker than that of the most effective in clinical practice antidyskinetic drug amantadine (20 mg/kg). However, after five days of treatment, the effect of hemantane injections exceeded that of amantadine.

Topics: Adamantane; Adrenergic Agents; Animals; Antiparkinson Agents; Dyskinesia, Drug-Induced; Levodopa; Male; Oxidopamine; Parkinsonian Disorders; Rats

The effects of acute and subchronic administration of antiparkinsonian drugs hemantane and amantadine on dopamine transporter (DAT) content in the brain of normal and MPTP-treated mice have been studied. MPTP treatment (30 mg/kg, daily for 2 days, i.p.) led to an insignificant decrease of the DAT level in striatum, while not influencing the DAT content in the frontal cortex of mice. The acute administration of hemantane (20 mg/kg, i.p.) failed to influence the DAT levels in the tested structures of mice brain, while amantadine (13.9 mg/kg, i.p) decreased the DAT level but only in striatum. The acute administration of a drug (hemantane or amantadine) simultaneously with MPTP toxin reduced the DAT levels in striatum but did change the DAT concentration in the frontal cortex. On the contrary, the subchronic injection of hemantane alone (7 x 20 mg/kg, i.p.) and in combination with the toxin increased the DAT levels in the brain structures, while amantadine (7 x 13.9 mg/kg, i.p.) led to a pronounced increase of DAT concentration only in the striatum. Thus, both similar and dissimilar trends in the neurochemical effects of hemantane and amantadine have been experimentally revealed.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Adamantane; Amantadine; Animals; Antiparkinson Agents; Brain; Dopamine Plasma Membrane Transport Proteins; Drug Synergism; Male; Mice; Mice, Inbred C57BL; Parkinsonian Disorders

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