Meta regression: Relationship between antipsychotic receptor binding profiles and side-effects

Olten, Baris; Bloch, Michael H.

doi:10.1016/j.pnpbp.2018.01.023

Cited by 35 publications

(22 citation statements)

References 44 publications

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“…The determination of receptor occupancy can be used not only to determine drug dosages required for AP efficacy but also to estimate the dose likely to induce adverse effects, such as hyperprolactinemia (15) and total side effect burden (16).…”

Section: Neurotransmitter Receptors and Sexmentioning

confidence: 99%

The Pharmacodynamics of Antipsychotic Drugs in Women and Men

Seeman

2021

Front. Psychiatry

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Background: Animal and human experiments have confirmed sex differences in the expression of hepatic enzymes that metabolize antipsychotic drugs and that may, in this way, be partly responsible for the clinical sex/gender differences observed in the efficacy and tolerability of antipsychotic treatment.Aim: The aim of this mini review is to synthesize the literature on the pharmacodynamics of male/female differential response to antipsychotic drugs.Method: Relevant search terms were used to search for pre-clinical and human trials and analysis of antipsychotic differential drug response and occurrence/severity of adverse effects in women and men.Results: The search found that sex influences drug response via the amount of a given drug that enters the brain and the number of neurotransmitter receptors to which it can bind. Consequently, sex partly determines the efficacy of a specific drug and its liability to induce unwanted effects. There are other factors that can overshadow or enhance the dimorphic effect of sex, for instance, the host's age, hormonal status, diet and life style as well as the molecular structure of the drug and its dose, and the method of its administration. Most of all, the host's individual genetics affects each step of a drug's pharmacodynamics.Conclusion: On average, women's psychotic symptoms respond to antipsychotic drugs at doses lower than men's. This means that many women may be de facto overdosed and, thus, experience unnecessary adverse effects. That being said, factors such as genetics and age probably determine drug response and tolerability to a greater degree than do biological sex or gender social roles.

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Section: Neurotransmitter Receptors and Sexmentioning

confidence: 99%

The Pharmacodynamics of Antipsychotic Drugs in Women and Men

Seeman

2021

Front. Psychiatry

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“…In women with psychosis (schizophrenia, delusional disorder, or mood disorder with psychotic features), side effects of the antipsychotic medication such as weight gain and hyperprolactinemia, 95 intensify naturally occurring menopausal symptoms. For instance, weight gain increases muscle and joint pain and heat intolerance.…”

Section: Hormones and Menopausementioning

confidence: 99%

The association between hormones and antipsychotic use: a focus on postpartum and menopausal women

González-Rodríguez

Seeman

2019

Therapeutic Advances in Psychopharmacology

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During the postpartum and menopausal periods of women’s lives, there is a well-established and significant drop of circulating estrogens. This may be the reason why both these periods are associated with an increased risk for onset or exacerbation of psychiatric disorders. Whether symptoms are mainly affective or mainly psychotic, these disorders are frequently treated with antipsychotic medications, which calls for an examination of the relationship between hormone replacement and antipsychotic agents at these time periods. The aim of this narrative review is to summarize what is known about the association of hormones and antipsychotics in the postnatal period and at menopause. In the review, we focus on estrogen and oxytocin hormones and include, for the most part, only papers published within the last 10 years. Both estradiol and oxytocin have at various times been implicated in the etiology of postpartum disorders, and estrogens, sometimes combined with progesterone, have been tested as potential treatments for these conditions. The role of estradiol as an adjunct to antipsychotics in the prevention of postpartum relapses is currently controversial. With respect to oxytocin, studies are lacking. Psychosis in menopausal and postmenopausal women has been successfully treated with estrogens and selective estrogen-receptor modulators, mainly raloxifene, in addition to antipsychotics. Some symptoms appear to respond better than others. No oxytocin study has specifically targeted postmenopausal women. Because of feedback mechanisms, there is a theoretical danger of therapy with exogenous hormones interfering with endogenous secretion and disturbing the balance among inter-related hormones. When used with antipsychotics, hormones may also affect the metabolism and, hence, the brain level of specific antipsychotics. This makes treatment with antipsychotics plus hormones complicated. Dose, timing and route of intervention may all prove critical to efficacy. While much remains unknown, this literature review indicates that, within standard dose ranges, the combination of hormones and antipsychotics for postnatal and menopausal women suffering severe mental distress can be beneficial, and is safe.

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“…A vast number of clinical studies has demonstrated that atypical antipsychotics can induce a series of adverse effects in the treatment of schizophrenia, such as weight gain, hyperglycaemia and QTc prolongation [ 18 , 19 , 20 ]. These adverse side effects have been proved to be associated with several off-target receptors, mainly focused on histamine H 1 , 5-HT 2C , and adrenergic α 1 [ 21 , 22 ].…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis and Biological Investigation of Flavone Derivatives as Potential Multi-Receptor Atypical Antipsychotics

et al. 2020

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The design of a series of novel flavone derivatives was synthesized as potential broad-spectrum antipsychotics by using multi-receptor affinity strategy between dopamine receptors and serotonin receptors. Among them, 7-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl) piperidin- 1-yl) butoxy)-2,2-dimethylchroman-4-one (6j) exhibited a promising preclinical profile. Compound 6j not only showed high affinity for dopamine D2, D3, and serotonin 5-HT1A, 5-HT2A receptors, but was also endowed with low to moderate activities on 5-HT2C, α1, and H1 receptors, indicating a low liability to induce side effects such as weight gain, orthostatic hypotension and QT prolongation. In vivo behavioral studies suggested that 6j has favorable effects in alleviating the schizophrenia-like symptoms without causing catalepsy. Taken together, compound 6j has the potential to be further developed as a novel atypical antipsychotic.

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Meta regression: Relationship between antipsychotic receptor binding profiles and side-effects

Cited by 35 publications

References 44 publications

The Pharmacodynamics of Antipsychotic Drugs in Women and Men

The Pharmacodynamics of Antipsychotic Drugs in Women and Men

The association between hormones and antipsychotic use: a focus on postpartum and menopausal women

Design, Synthesis and Biological Investigation of Flavone Derivatives as Potential Multi-Receptor Atypical Antipsychotics

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