The D 2 dopamine receptor occupancy of risperidone and its relationship to extrapyramidal symptoms: A pet study

Abstract

Risperidone is a recently introduced neuroleptic distinguished by a decreased incidence of extrapyramidal side effects (EPS). The mechanism of its low EPS is unclear. Since it has been shown that EPS is related to the level of D 2 receptor occupancy, we studied nine patients receiving 2–6 mg/day of risperidone using [ 11C]-raclopride PET scans in order to determine the in vivo D 2 receptor binding characteristics of risperidone. The mean level of receptor occupancy was 66% at 2 mg; 73% at 4 mg; and 79% at 6 mg. Three patients, those with the highest receptor occupancies, exhibited mild EPS, though none required anitparkinsonian medications. Our results suggest that at doses of 4–6 mg the in vivo D 2 receptor occupancy of risperidone is similar to that of typical neuroleptics and higher than that of clozapine. This would suggest that the EPS benefits of risperidone cannot be explained by a low D 2 binding but may be related to its high 5-HT 2 affinity. However, the emergence of EPS at higher levels of D 2 receptor occupancy, in this study and in previous clinical trials, would suggest that risperidone's high 5-HT 2 affinity provides only a relative protection from EPS. and once the D 2 occupancy exceeds a certain threshold this ‘relative’ 5-HT 2-mediated protection from EPS may be lost.