Determination of functionally-relevant serum levels of MJ 13859-1 in the dog: relationship to blockade of amphetamine stereotypy.

The ability of drugs to block dopamine-agonist induced stereotypy in animals has proven to be a reliable in vivo predictor of antipsychotic efficacy in man. Assessment of a drug's potency at displacing [3H]spiperone from rat striatal membranes is an in vitro test which also has predictive validity for antipsychotic actions. Methods are described for assessing stereotyped behavior in the dog, and for measuring the ability of serum samples taken from treated animals at behaviorally interesting time points, to displace [3H]spiperone from washed synaptic membranes of rat striata. In these studies, oral administration of the potential antipsychotic agent MJ 13859-1 blocked amphetamine-induced stereotyped behavior in the dog for 6 hours. This behavioral effect was accompanied by sustained serum levels of [3H]spiperone displacing moieties derived from MJ 13859-1.