THE PROFILE OF SABCOMELINE (SB-202026), A FUNCTIONALLY SELECTIVE M-1 RECEPTOR PARTIAL AGONIST, IN THE MARMOSET

1 Sabcomeline (SB-202026, 0.03 mg kg(-1), p.o.), a potent and function ally selective M-1 receptor partial agonist, caused a statistically si gnificant improvement in the performance of a visual object discrimina tion task by marmosets. No such improvement was seen after RS86 (0.1 m g kg(-1), p.o.). 2 Initial learning, which only required an associatio n of object with reward and an appropriate response to be made, was no t significantly affected. Reversal learning, which required both the e xtinction of the previously learned response and the acquisition of a nevi response strategy, was significantly improved after administratio n of sabcomeline (0.03 mg kg(-1), p.o.). 3 Sabcomeline (0.03 and 0.1 m g kg(-1), p.o.) had no significant effect on mean blood pressure measu red for 2 h after administration in the conscious marmoset. 4 Sabcomel ine (0.03 mg kg(-1), p.o.) caused none of the overt effects such as em esis or behaviours often seen after the administration of muscarinic a gonists, e.g. face rubbing and licking. 5 This is the first study to d emonstrate cognitive enhancement by a functionally selective Mi recept or partial agonist in a normal (i.e. non-cognitively impaired) non-hum an primate and this effect was seen at a dose which did not cause side effects. 6 Perseverative behaviour and deficient acquisition of new i nformation are seen in patients with Alzheimer's disease (AD). Therefo re the data suggest that sabcomeline might be of therapeutic benefit i n the treatment of AD.