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The profile of sabcomeline (SB‐202026), a functionally selective M 1 receptor partial agonist, in the marmoset
Author(s) -
Harries M H,
Samson N A,
Cilia J,
Hunter A J
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701844
Subject(s) - partial agonist , agonist , marmoset , licking , endocrinology , extinction (optical mineralogy) , medicine , receptor , pharmacology , psychology , neuroscience , chemistry , biology , paleontology , mineralogy
Sabcomeline (SB‐202026, 0.03 mg kg −1 , p.o.), a potent and functionally selective M 1 receptor partial agonist, caused a statistically significant improvement in the performance of a visual object discrimination task by marmosets. No such improvement was seen after RS86 (0.1 mg kg −1 , p.o.). Initial learning, which only required an association of object with reward and an appropriate response to be made, was not significantly affected. Reversal learning, which required both the extinction of the previously learned response and the acquisition of a new response strategy, was significantly improved after administration of sabcomeline (0.03 mg kg −1 , p.o.). Sabcomeline (0.03 and 0.1 mg kg −1 , p.o.) had no significant effect on mean blood pressure measured for 2 h after administration in the conscious marmoset. Sabcomeline (0.03 mg kg −1 , p.o.) caused none of the overt effects such as emesis or behaviours often seen after the administration of muscarinic agonists, e.g. face rubbing and licking. This is the first study to demonstrate cognitive enhancement by a functionally selective M 1 receptor partial agonist in a normal (i.e. non‐cognitively impaired) non‐human primate and this effect was seen at a dose which did not cause side effects. Perseverative behaviour and deficient acquisition of new information are seen in patients with Alzheimer's disease (AD). Therefore the data suggest that sabcomeline might be of therapeutic benefit in the treatment of AD.