[COMPARISON OF CYTOPROTECTIVE EFFECTS OF HEMANTANE AND AMANTADINE UNDER CONDITIONS OF 6-HYDROXYDOPAMINE NEUROTOXIN ACTION ON CULTURED HUMAN NEUROBLASTOMA CELLS].

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.

[Influence of hemantane in injectable dosage form on levodopa-induced dyskinesia in rats with model parkinsonian syndrome].

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.

[Comparative study of himantane and amantadine effects in experimental intracerebral posttraumatic hematoma].

Effects of the novel antiparkinsonian drug himantane and amantadin were studied in rats with intracerebral posttraumatic hematoma. Drugs were administered first at 3.5 hours after surgery and then for 4 consecutive days. Effects were registered on days 1, 3, 7 and 14 after surgery. It was shown that both drugs significantly decreased mortality and improved motor activity, exploratory behavior and memory. Amantadin was more effective in tests for motor activity and exploratory behavior. Himantane 5 mg/kg i.p demonstrated the more pronounced activity in restoring memory. The results obtained testify for neuroprotective properties of the novel antiparkinsonian drug himantane.

[Study of hemantane effects in rats on a model of early (premotor) stage of Parkinson's disease].

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.

[Comparative study of amantadine and hemantane effects on development of levodopa-induced dyskinesia in rat model of parkinsonian syndrome].

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.