clozapine and serpentine-(alkaloid)

Negative symptoms of schizophrenia are particularly problematic due to their deleterious impact on a patient's social life. The indol alkaloid alstonine, the major component of traditional remedies used for treating mental illnesses in Nigeria, presents a clear antipsychotic-like profile in mice, as well as anxiolytic properties. Considering that social interaction is the core of negative symptoms, and that anxiolytic drugs can improve social interaction behavior, the aim of this study was to evaluate the effects of alstonine in the social interaction and MK801-induced social withdrawal models in mice. Sub-chronic (but not acute) treatment with alstonine 0.5 mg/kg (but not 1.0 mg/kg) significantly increased social interaction in mice. Moreover, MK801-induced social withdrawal was completely prevented by sulpiride (10 mg/kg) and alstonine 1.0 mg/kg, and partially prevented by alstonine 0.5 mg/kg. The study indicates that alstonine not only increases social interaction in normal mice, but also averts social deficits attributable to negative symptoms of schizophrenia. This study reinforces and complements the antipsychotic-like profile of alstonine, and emphasizes its potential as a drug useful for the management of negative symptoms in schizophrenia.

Topics: Animals; Anti-Anxiety Agents; Antipsychotic Agents; Clozapine; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Haloperidol; Interpersonal Relations; Male; Mice; Motor Activity; Secologanin Tryptamine Alkaloids; Social Behavior Disorders; Sulpiride

Psychiatry co-morbidity with epilepsy is common and often requires the combined use of psychotropic and antiepileptic drugs (AEDs). For schizophrenic patients, the occurrence of seizures with atypical agents is highest among antipsychotics, although these agents are more effective in alleviating symptoms (including negative symptoms) and are associated with fewer extrapiramidal effects. The indol alkaloid alstonine is the major component of plants used by traditional Nigerian psychiatrists as anti-dementia drugs. The alkaloid presents an experimental profile very similar to the atypical antipsychotic clozapine. This study aimed to compare the pro-convulsant activity of these two antipsychotic compounds. Through repetitive administration over a 30-day period in a kindling paradigm, it is shown that, unlike clozapine, alstonine does not possess pro-convulsant activity. The data adds to previous suggestions that alstonine deserves to be scrutinized as a model for the development of newer antipsychotics.

Topics: Animals; Anticonvulsants; Antipsychotic Agents; Apocynaceae; Clozapine; Male; Mice; Mice, Inbred Strains; Phytotherapy; Plant Extracts; Secologanin Tryptamine Alkaloids; Seizures