Possible Interaction: Clozapine and Cocaine

“In spite of this elevation in blood levels, clozapine pretreatment had a significant diminishing effect upon subjective responses to cocaine , including 'expected high', 'high' and 'rush', notably at the 50 mg dose.”

“ Cocaine- or MK-801-induced hyperactivity in animals was markedly inhibited by KKHA-761 or clozapine.”

“In summary, acute studies (a) support previous data from this laboratory and others that cocaine acts as … the monoamines, DA and 5-HT and on locomotor behavior as well and (b) show that clozapine , 5-HT(2)/DA(2) antagonist, blocked …-HT and psychomotor stimulant behavior induced by cocaine.”

“A decrease in that response was also found in animals treated repeatedly with cocaine (days 1-5) and challenged with the psychostimulant combined with clozapine (10 mg/kg, but not 2.5-5 mg/kg) on day 10.”

“The obtained results indicate the ability of clozapine to reduce both acute and sensitizing locomotor responses to cocaine.”

“When given in combination with acute cocaine, clozapine (10 mg/kg, but not 2.5-5 mg/kg) attenuated the locomotor effects of the psychostimulant.”

“Similar decreases in cocaine self-administration rates were obtained with the dopamine receptor antagonists olanzapine, clozapine , risperidone, fluphenazine and haloperidol.”

“A higher dose of CLZ decreased cocaine self-administration in an apparently nonspecific manner.”

“In combination … of cocaine in the … AJ and CLZ decreased drug appropriate responding by at least 50% in two of four monkeys, but had little or no effect in … up to doses that completely suppressed lever pressing (6.4 mg/kg of AJ; 3.2 mg/kg of CLZ).”

“Taken together, the present findings suggest that any blockade of the reinforcing and discriminative stimulus effects of cocaine by AJ and CLZ was, at best, partial.”