Partial agonists of dopamine receptors: receptor theory and the dopamine hypothesis of psychosis

Pimm²

2021

Self Cite

SUMMARY Aripiprazole, brexpiprazole and cariprazine are partial dopamine (and serotonin) agonists developed as novel antipsychotics. This article discusses their pharmacology, evidence on their licensed and off-licence uses (including psychosis, mania, bipolar depression, Tourette syndrome and autism spectrum disorder) and side-effects. In schizophrenia, they have a low risk of Parkinsonism or hyperprolactinaemia, cause modest increases in body weight and are of moderate efficacy.

“…They have 'intrinsic activity' as agonists, a property explained in our previous article (Cookson 2021).…”

Section: Pharmacologymentioning

confidence: 90%

Section: Pharmacologymentioning

confidence: 99%

mentioning

confidence: 99%

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Partial agonists of dopamine receptors: mechanisms and clinical effects of aripiprazole, brexpiprazole and cariprazine

Pimm²

2021

Self Cite

“…Finally, to add further reason to the rhyme of prescribing antipsychotics, a series of papers address the use of partial agonists at dopamine receptors and alone or in combination with other antipsychotics (Cookson 2023a(Cookson , 2023b(Cookson , 2023c(Cookson , 2023d.…”

Section: Autism Spectrum Disordersmentioning

confidence: 99%

Rhyme or reason in therapeutics

Pimm²

2023

Self Cite

“…In three other articles in this issue we review the nature of partial agonism of dopamine receptors (Cookson 2023a) and the qualities of three partial agonists, aripiprazole, brexpiprazole and cariprazine (Cookson 2023b), and discuss the combination of a partial agonist with a full antagonist (Cookson 2023c).…”

Section: Learning Objectivesmentioning

confidence: 99%

Partial agonists of dopamine receptors: theoretical principles of combining antipsychotics including partial agonists to treat schizophrenia

Pimm²,

Brentnall³

2022

SUMMARY Partial agonists such as aripiprazole are often used in addition to a full antagonist such as amisulpride, risperidone or olanzapine in an attempt to mitigate side-effects such as sedation, hyperprolactinaemia and weight gain. However, there can be unintended consequences, including worsening of psychosis. Moreover, previous exposure to a partial agonist may impair the subsequent response to a potent antipsychotic such as haloperidol used to control symptoms of relapse. To understand the mechanisms involved, a method is needed to compare potency in the pharmacological effects of different drugs used in combinations. This article is intended to explore and explain the theoretical principles based on the dopamine hypothesis of schizophrenia. We apply the method to analyse a recently described trial in which two full antagonists (olanzapine and amisulpride) are compared individually and in combination.