Studies on anticonvulsant actions of L-deprenyl.

L-Deprenyl (Selegeline) introduced for use in parkinson's disease, is implicated to show beneficial effects in epilepsy, alzheimer's disease, cognition, depression and other age related neurological diseases. In this study, we investigated the CNS effects of L-deprenyl with special reference to epilepsy, anxiety and cognition and memory in mice. L-deprenyl (10, 20 and 40 mg/kg) showed a significant anticonvulsant activity against pentylenetetrazole (PTZ)-induced convulsions. Combination of L-deprenyl (10 mg/kg) with the sub-protective dose of diazepam (1 mg/kg) showed potentiation of the anticonvulsant effect. In the maximal-electroshock (MES)-induced convulsions, L-deprenyl (10 mg/kg) significantly delayed the onset and decreased the duration of extensor phase. Its combination with the lower dose of phenytoin (10 mg/kg) showed potentiation in response compared to the per se effect of both the drugs. However, L-deprenyl did not show any protective effect in lithium-pilocarpine induced status epilepticus. Acute treatment with L-deprenyl had no effect on learning and memory. In chronic treatment, L-deprenyl per se showed no effect on learning and memory but did improve the condition in mice with scopolamine induced memory deficit. L-Deprenyl per se was anxiogenic though in combination with diazepam (1 mg/kg) it potentiated the antianxiety effect of the latter. The above observations suggest that in epilepsy, L-deprenyl might be acting partially by influencing the GABAA/benzodiazepine mechanism in the brain (similar to diazepam and phenytoin), and in cognition enhancing effect, the cholinergic system might be playing a role. Thus, L-deprenyl could prove to be an adjuvant in the antiepileptic therapy and beneficial in dementia associated with epilepsy.

Role of selegiline as initial monotherapy in early Parkinson's disease.

Twenty patients of Idiopathic Prakinson's disease in the early phase were enrolled to study the efficacy and safety of selegiline as monotherapy. The mean duration of time before levodopa had to be initiated was 9.75 months. The UPDRS scores for activities of daily living, motor examination, tremor and total score showed significant improvement initially with subsequent worsening. Selegiline was well tolerated and there were no serious side-effects. In conclusion, selegiline may have a short lasting symptomatic effect in IPD and is well tolerated.

Combination therapy of parkinsonism with deprenyl.

In view of the encouraging results in various trials with deprenyl as an added drug therapy for Parkinson's disease, a pilot study to study deprenyl's efficacy in the Indian population was undertaken. Eleven patients were recruited in this open trial and were objectively assessed by Unified Rating Scale for Parkinsonism of Columbia University, Modified Hoehn and Yahr Staging and Schwab and England activities of daily living. Side effects, mood changes, changes in dyskinesia percentage, early morning dystonia and off period percentage were also noted. This study suggests improvement in the above parameters with minimal side effects.

L-deprenyl therapy in Thai patients with Parkinson's disease: before and after, clinical trial of 50 patients.

Fifty Thai patients with Parkinson's disease of all staging were allocated for 10 mg/day L-deprenyl therapy as the monotherapy (6 patients) and adjunctive therapy for at least two months. The assessment of this open study included the activities of daily living using Schwab/England Scale, Hoehn and Yahr staging and Unified Parkinson Disease Rating Scale (UPDRS) by comparison of the initial and after two month of treatment scores. There was improvement of both Schwab/England Scale and UPDRS in Hoehn and Yahr stage I, II and III patients. In stage IV and V patients there was no benefit of L-deprenyl therapy of both clinical and statistical analyses. Adverse effects of L-deprenyl were not serious. There were dry mouth (20%), anorexia (10%), nausea and vomiting (8%), insomnia (6%), lightheadedness (4%) constipation (4%), abdominal pain (2%), generalised ache (2%). We conclude that L-deprenyl therapy is effective, safe, but costly. It is more effective in early Parkinsonism. The effectiveness of L-deprenyl is less in more advanced states of Parkinson's disease. Thus, selection of the appropriate Parkinsonian patient for L-deprenyl therapy is vital.