title: The adenosine A2A receptor agonist CGS 21680 exhibits antipsychotic-like activity in Cebus apella monkeys.
abstract: 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.
authors.affiliation: Sct. Hans Hospital, Research Institute of Biological Psychiatry, DK-4000 Roskilde, Denmark. maibritt.b.andersen@shh.hosp.dk
authors.forename: M B
authors.initials: MB
authors.lastname: Andersen
authors.forename: K
authors.initials: K
authors.lastname: Fuxe
authors.forename: T
authors.initials: T
authors.lastname: Werge
authors.forename: J
authors.initials: J
authors.lastname: Gerlach
mesh_terms: 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
chemical_list: 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