STUDIES ON STEREOSELECTIVE DOPAMINE RECEPTOR BLOCKADE IN RAT-BRAIN BY RIGID SPIRO AMINES

The effects of two series of tetracyclic spiro amines and of chlorpromazine, clozapine and sulpiride on (3H)-spiroperidol binding in various dopamine areas of the brain and on apomorphine induced stereotypies and hyperactivity was studied in rats. The two series of rigid spiro amines (racemates and enantiomers) were found to exhibit stereoselective effects on (3H)-spiroperidol binding and on apomorphine induced behaviours, thus providing evidence for stereospecific dopamine receptor blockade. Of the four enantiomers of the spiro amines only one (cis-(-)) showed a high potency, higher than that of chlorpromazine, clozapine and sulpiride. Sulpiride was a weak inhibitor of (3H)-spiroperidol binding and was less active in limbic areas than in the striatum. The potencies of the spiro amines as well as of chlorpromazine and clozapine in displacing (3H)-spiroperidol in the striatum and in the limbic dopamine system (nucleus accumbens and tuberculum olfactorium) correlated closely with their potencies in inhibiting apomorphine induced stereotypies and hyperactivity. © 1978.