OBJECTIVE: Loxapine, a dibenzoxazepine antipsychotic, is closely related to clozapine and shares clozapine's high affinity for binding to serotonin 5-HT2 and dopamine D4 receptors. The purpose of this study was to document loxapine's 5-HT2 and D2 receptor occupancy in vivo in patients with psychoses. METHOD: Ten patients who were taking loxapine (10-100 mg/day) had their D2 and 5-HT2 receptors assessed by means of positron emission tomography with [11C]raclopride and [18F]setoperone, respectively. RESULTS: The D2 receptor occupancy ranged from 43% to 90%; 5-HT2 occupancy varied from 27% to near saturation. Statistical comparison of the results showed that loxapine was equipotent in blocking 5-HT2 and D2 receptors. CONCLUSIONS: Loxapine differs from typical neuroleptics in demonstrating a high degree of 5-HT2 receptor occupancy. However, it is not "atypical" like clozapine and risperidone, since its 5-HT2 occupancy is not higher than its D2 occupancy. The results demonstrate that a high level of 5-HT2 occupancy is not a sufficient condition for atypicality. If atypical antipsychotic action is predicated on a combination of 5-HT2 and D2 effects, then it requires > 80% 5-HT2 occupancy in conjunction with < 80% D2 occupancy.
OBJECTIVE:Loxapine, a dibenzoxazepine antipsychotic, is closely related to clozapine and shares clozapine's high affinity for binding to serotonin 5-HT2 and dopamine D4 receptors. The purpose of this study was to document loxapine's 5-HT2 and D2 receptor occupancy in vivo in patients with psychoses. METHOD: Ten patients who were taking loxapine (10-100 mg/day) had their D2 and 5-HT2 receptors assessed by means of positron emission tomography with [11C]raclopride and [18F]setoperone, respectively. RESULTS: The D2 receptor occupancy ranged from 43% to 90%; 5-HT2 occupancy varied from 27% to near saturation. Statistical comparison of the results showed that loxapine was equipotent in blocking 5-HT2 and D2 receptors. CONCLUSIONS:Loxapine differs from typical neuroleptics in demonstrating a high degree of 5-HT2 receptor occupancy. However, it is not "atypical" like clozapine and risperidone, since its 5-HT2 occupancy is not higher than its D2 occupancy. The results demonstrate that a high level of 5-HT2 occupancy is not a sufficient condition for atypicality. If atypical antipsychotic action is predicated on a combination of 5-HT2 and D2 effects, then it requires > 80% 5-HT2 occupancy in conjunction with < 80% D2 occupancy.
Authors: Kristen J Brennand; Anthony Simone; Jessica Jou; Chelsea Gelboin-Burkhart; Ngoc Tran; Sarah Sangar; Yan Li; Yangling Mu; Gong Chen; Diana Yu; Shane McCarthy; Jonathan Sebat; Fred H Gage Journal: Nature Date: 2011-04-13 Impact factor: 49.962
Authors: Jessica A Hellings; Gregory Reed; Sharon E Cain; Xinghua Zhou; Francis X Barth; Michael G Aman; Gladys I Palaguachi; Dmytro Mikhnev; Rujia Teng; Rebecca Andridge; Marilyn Logan; Merlin G Butler; Joan C Han Journal: J Child Adolesc Psychopharmacol Date: 2015-03 Impact factor: 2.576