2-(4-(2-carboxyethyl)phenethylamino)-5--n-ethylcarboxamidoadenosine and Basal-Ganglia-Diseases

The adenosine A2A receptor agonist CGS 21680 has shown effects similar to dopamine antagonists in behavioural assays in rats predictive for antipsychotic activity, without induction of extrapyramidal side-effects (EPS). In the present study, we examined whether this functional dopamine antagonism and lack of EPS in rodents could also be observed in non-human primates. We investigated the effects of CGS 21680 on behaviours induced by D-amphetamine and (-)-apomorphine in EPS-sensitized Cebus apella monkeys. CGS 21680 was administered s.c. in doses of 0.01, 0.025 and 0.05 mg/kg, alone and in combination with D-amphetamine and (-)-apomorphine. The monkeys were videotaped after drug administration and the tapes were rated for EPS and psychosis-like symptoms. CGS 21680 decreased apomorphine-induced behavioural unrest, arousal (0.01-0.05 mg/kg) and stereotypies (0.05 mg/kg) while amphetamine-induced behaviours (unrest, stereotypies, arousal) were unaffected. EPS were not observed at any dose. At 0.05 mg/kg CGS 21680 produced vomiting. The two lower doses did not produce observable side-effects. Though the differential effect on amphetamine- and apomorphine-induced behaviours is intriguing, CGS 21680 showed a functional anti-dopaminergic effect in Cebus apella monkeys without production of EPS. This further substantiates that adenosine A2A receptor agonists may have potential as antipsychotics with atypical profiles.

Topics: Adenosine; Amphetamine; Animals; Antipsychotic Agents; Apomorphine; Arousal; Basal Ganglia Diseases; Behavior, Animal; Cebus; Conscious Sedation; Dopamine Agonists; Dopamine Antagonists; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Male; Motor Activity; Phenethylamines; Purinergic P1 Receptor Agonists; Receptor, Adenosine A2A; Stereotyped Behavior