ABSTRACT
Although recently developed drugs have brought significant improvement, the treatment of psychotic disorders still presents serious drawbacks. Since inherent complexity and lack of satisfactory understanding of the underlying pathophysiology impose limits for rational drug design, resourceful approaches in the search for antipsychotics are pertinent. This paper reports pharmacological properties of alstonine, a heteroyohimbine type alkaloid, Which exbitited an antipsychotic-like profile, inhibiting amphetamine-induced lethaly, apomorphine-induced steotypy and potentiating barbiturate-induced slleping time. Atypical features of alstonine were the prevention of haloperidol-induced catalepsy and lack of direct interaction with D1, D2 and 5-HT2A receptors, classically linked to antipsychotic mechanism of action.
Subject(s)
Animals , Male , Mice , Antipsychotic Agents/pharmacology , Plants, Medicinal , Secologanin Tryptamine Alkaloids/pharmacology , Amphetamine/antagonists & inhibitors , Apomorphine/antagonists & inhibitors , Barbiturates/antagonists & inhibitors , Central Nervous System Stimulants/antagonists & inhibitors , Chlorpromazine/pharmacology , Clozapine/pharmacology , Diazepam/pharmacology , Emetics/antagonists & inhibitors , Haloperidol/pharmacology , Hypnotics and Sedatives/antagonists & inhibitors , Nigeria , Pentobarbital/pharmacology , Reserpine/pharmacology , Sleep/drug effects , Stereotyping , Sulpiride/pharmacologyABSTRACT
Ascorbic acid (1 g/kg) accentuated anorectic and locomotor effects of amphetamine (5 mg/kg) and delayed development of tolerance to anorectic effect. On the contrary, it did not alter the pattern of reverse tolerance to increased locomotor activity. The results suggest that modulation of dopamine receptor sensitivity by ascorbic acid may be the reason for the delay in development of tolerance to amphetamine induced anorexia.
Subject(s)
Amphetamine/antagonists & inhibitors , Animals , Anorexia/chemically induced , Ascorbic Acid/pharmacology , Drug Tolerance , Male , Motor Activity/drug effects , Rats , Rats, WistarABSTRACT
Effects of single oral administration of isoproturon (0.5, 1.0 and 2.0 g/kg) on CNS of male mice were studied. At higher doses, spontaneous motor activity (SMA) and forced locomotor activity (FLA) were reduced. Reduction of SMA and FLA was lesser than the reference drug-chlorpromazine hydrochloride (Ch. HCl; 15 mg/kg). Isoproturon, at all doses, potentiated both pentobarbital and barbital-induced sleeping time. At higher doses, potentiation of pentobarbital-induced hypnosis was comparable to Ch.HCl but isoproturon was more effective in inducing hypnosis with barbital. Isoproturon could not protect mice against amphetamine-induced aggregation toxicity. Isoproturon exhibited anticonvulsant activity against both supramaximal electroshock seizures and pentylenetetrazol-induced convulsions. It had no anticonvulsant activity against strychnine but only caused delay in onset of and protection from mortality. At higher doses, anticonvulsant action of isoproturon was comparable to diphenylhydantoin (50 mg/kg) and phenobarbital sodium (100 mg/kg). The study reveals that isoproturon has distinct inhibitory effect on central motor performance and sedative action on CNS. And also it has anticonvulsive and protective actions.