Brexpiprazole has a low risk of dopamine D 2 receptor sensitization and inhibits rebound phenomena related to D 2 and serotonin 5-HT 2A receptors in rats
Long-term antipsychotic treatment in patients with schizophrenia can induce supersensitivity psychosis and tardive dyskinesia which is thought to be caused by dopamine D receptor sensitization. We evaluated the effects of brexpiprazole on D receptor sensitivity after subchronic treatment in rats. We...
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Published in | Neuropsychopharmacology reports Vol. 39; no. 4; pp. 279 - 288 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
John Wiley & Sons, Inc
01.12.2019
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Subjects | |
Online Access | Get full text |
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Summary: | Long-term antipsychotic treatment in patients with schizophrenia can induce supersensitivity psychosis and tardive dyskinesia which is thought to be caused by dopamine D
receptor sensitization. We evaluated the effects of brexpiprazole on D
receptor sensitivity after subchronic treatment in rats. We also evaluated whether brexpiprazole could suppress enhanced response to D
receptors in rats subchronically dosed with another atypical antipsychotic.
The maximum D
receptor density (B
) and apomorphine (a D
receptor agonist)-induced stereotypy were measured in rats orally dosed with vehicle, haloperidol (1 mg/kg), or brexpiprazole (4 or 30 mg/kg for B
, 6 or 30 mg/kg for stereotypy) for 21 days. Then, effects of oral administrations of brexpiprazole (3 mg/kg), aripiprazole (10 mg/kg), and olanzapine (3 mg/kg) against increases in apomorphine-induced hyperlocomotion and (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI: a 5-HT
receptor agonist)-induced head twitches were evaluated in rats subcutaneously treated with risperidone (1.5 mg/kg/d) via minipumps for 21 days.
Haloperidol and brexpiprazole (30 mg/kg: approximately tenfold ED
of anti-apomorphine-induced stereotypy) but not brexpiprazole (4 or 6 mg/kg) significantly increased the B
and apomorphine-induced stereotypy. Brexpiprazole (3 mg/kg) and olanzapine (3 mg/kg) significantly suppressed both increases in apomorphine-induced hyperlocomotion and also DOI-induced head twitches in rats subchronically treated with risperidone, but aripiprazole (10 mg/kg) significantly suppressed only apomorphine-induced hyperlocomotion.
Brexpiprazole has a low risk of D
receptor sensitization after a repeated administration and suppresses the rebound phenomena related to D
and 5-HT
receptors after a repeated administration of risperidone. |
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ISSN: | 2574-173X 2574-173X |
DOI: | 10.1002/npr2.12076 |