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Roxindole, a potential antidepressant. I. Effect on the dopamine system
J Maj1, K Kolodziejczyk, Z Rogóz
1Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Journal of Neural Transmission (Vienna, Austria : 1996)
|January 1, 1996
Summary
Roxindole, a potential antipsychotic, demonstrates antidepressant and antiparkinsonian effects by influencing the dopamine system. It reduced immobility in rats and mice without causing extrapyramidal side-effects.
Area of Science:
- Neuropharmacology
- Dopamine System Research
- Drug Discovery
Background:
- Roxindole (EMD 49980) is a selective dopamine autoreceptor agonist with potential antipsychotic and clinical antidepressant efficacy.
- Understanding its neuropharmacological profile is crucial for evaluating its therapeutic potential.
Purpose of the Study:
- To investigate the neuropharmacological profile of roxindole in rats and mice.
- To assess its influence on the dopamine system and its potential antidepressant and antiparkinsonian activities.
- To evaluate its propensity for inducing extrapyramidal side-effects.
Main Methods:
- Administration of roxindole to male Wistar rats and male Albino Swiss mice.
- Assessment of locomotor activity, stereotypy, climbing behavior, and catalepsy.
- Evaluation of effects on amphetamine-, apomorphine-, quinpirole-, and reserpine-induced behaviors.
- Analysis of immobility time in the forced swimming test.
- Repeated administration (14 days) to assess long-term effects on D-amphetamine-induced hyperlocomotion.
Main Results:
- Low doses of roxindole decreased locomotor activity; higher doses did not induce hyperactivity or stereotypy.
- Roxindole antagonized various dopamine-mediated behaviors, including amphetamine- and apomorphine-induced effects, and reserpine-induced akinesia.
- It inhibited quinpirole-induced hyperlocomotion and antagonized haloperidol-, spiperone-, and fluphenazine-induced catalepsy.
- Roxindole reduced immobility in the forced swimming test and increased D-amphetamine-induced hyperlocomotion after repeated administration.
- The drug did not induce catalepsy when administered alone.
Conclusions:
- Roxindole exhibits potential antidepressant and antiparkinsonian activities.
- Its neuropharmacological profile suggests it may be devoid of extrapyramidal side-effects, differentiating it from typical antipsychotics.
- Roxindole warrants further investigation as a therapeutic agent for depression and Parkinson's disease.