The adenosine A2A receptor agonist CGS 21680 exhibits antipsychotic-like activity in Cebus apella monkeys.
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.
Andersen
M B
MB
Sct. Hans Hospital, Research Institute of Biological Psychiatry, DK-4000 Roskilde, Denmark. maibritt.b.andersen@shh.hosp.dk
Fuxe
K
K
Werge
T
T
Gerlach
J
J
D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000661:Amphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents; D001058:Apomorphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001143:Arousal / Q000187:drug effects; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D002428:Cebus; D016292:Procedural Sedation; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010627:Phenethylamines / Q000009:adverse effects / Q000494:pharmacology*; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D013239:Stereotyped Behavior / Q000187:drug effects
D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000661:Amphetamine; D000241:Adenosine; D001058:Apomorphine