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The role of histaminergic H1 and H3 receptors in food intake: a mechanism for atypical antipsychotic-induced weight gain?

Abstract

Atypical antipsychotics such as olanzapine and clozapine are effective at treating the multiple domains of schizophrenia, with a low risk of extra-pyramidal side-effects. However a major downfall to their use is metabolic side-effects particularly weight gain/obesity, which occurs by unknown mechanisms. The present paper explores the potential candidature of histaminergic neurotransmission in the mechanisms of atypical antipsychotic-induced weight gain, with a focus on the histaminergic H1 and H3 receptors. Olanzapine and clozapine have a high affinity for the H1 receptor, and meta-analyses show a strong correlation between risk of weight gain and H1 receptor affinity. In addition, olanzapine treatment decreases H1 receptor binding and mRNA expression in the rat hypothalamus. Furthermore, a complex role is emerging for the histamine H3 receptor in the control of hunger. The H3 receptor is a pre-synaptic autoreceptor that inhibits the synthesis and release of histamine, and a heteroreceptor that inhibits other neurotransmitters such as serotonin (5-HT), noradrenaline (NA) and acetylcholine (ACh), which are also implicated in the regulation of food intake. Thus, the H3 receptor is in a prime position to regulate food intake, both through its control of histamine and its influence on other feeding pathways. We proposed that a mechanism for atypical antipsychotic-induced weight gain may be partly through the H3 receptor, as a drug-induced decrease in H1 receptor activity may decrease histamine tone through the H3 autoreceptors, compounding the weight gain problem. In addition, atypical antipsychotics may affect food intake by influencing 5-HT, NA and ACh release via interactions with the H3 heteroreceptor.

Authors+Show Affiliations

Centre for Translational Neuroscience, School of Health Sciences, University of Wollongong, Wollongong, 2522, NSW, Australia. chao@uow.edu.auNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

19922755

Citation

Deng, Chao, et al. "The Role of Histaminergic H1 and H3 Receptors in Food Intake: a Mechanism for Atypical Antipsychotic-induced Weight Gain?" Progress in Neuro-psychopharmacology & Biological Psychiatry, vol. 34, no. 1, 2010, pp. 1-4.
Deng C, Weston-Green K, Huang XF. The role of histaminergic H1 and H3 receptors in food intake: a mechanism for atypical antipsychotic-induced weight gain? Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(1):1-4.
Deng, C., Weston-Green, K., & Huang, X. F. (2010). The role of histaminergic H1 and H3 receptors in food intake: a mechanism for atypical antipsychotic-induced weight gain? Progress in Neuro-psychopharmacology & Biological Psychiatry, 34(1), 1-4. https://doi.org/10.1016/j.pnpbp.2009.11.009
Deng C, Weston-Green K, Huang XF. The Role of Histaminergic H1 and H3 Receptors in Food Intake: a Mechanism for Atypical Antipsychotic-induced Weight Gain. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Feb 1;34(1):1-4. PubMed PMID: 19922755.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of histaminergic H1 and H3 receptors in food intake: a mechanism for atypical antipsychotic-induced weight gain? AU - Deng,Chao, AU - Weston-Green,Katrina, AU - Huang,Xu-Feng, Y1 - 2009/11/14/ PY - 2009/08/02/received PY - 2009/11/10/revised PY - 2009/11/11/accepted PY - 2009/11/20/entrez PY - 2009/11/20/pubmed PY - 2010/4/8/medline SP - 1 EP - 4 JF - Progress in neuro-psychopharmacology & biological psychiatry JO - Prog Neuropsychopharmacol Biol Psychiatry VL - 34 IS - 1 N2 - Atypical antipsychotics such as olanzapine and clozapine are effective at treating the multiple domains of schizophrenia, with a low risk of extra-pyramidal side-effects. However a major downfall to their use is metabolic side-effects particularly weight gain/obesity, which occurs by unknown mechanisms. The present paper explores the potential candidature of histaminergic neurotransmission in the mechanisms of atypical antipsychotic-induced weight gain, with a focus on the histaminergic H1 and H3 receptors. Olanzapine and clozapine have a high affinity for the H1 receptor, and meta-analyses show a strong correlation between risk of weight gain and H1 receptor affinity. In addition, olanzapine treatment decreases H1 receptor binding and mRNA expression in the rat hypothalamus. Furthermore, a complex role is emerging for the histamine H3 receptor in the control of hunger. The H3 receptor is a pre-synaptic autoreceptor that inhibits the synthesis and release of histamine, and a heteroreceptor that inhibits other neurotransmitters such as serotonin (5-HT), noradrenaline (NA) and acetylcholine (ACh), which are also implicated in the regulation of food intake. Thus, the H3 receptor is in a prime position to regulate food intake, both through its control of histamine and its influence on other feeding pathways. We proposed that a mechanism for atypical antipsychotic-induced weight gain may be partly through the H3 receptor, as a drug-induced decrease in H1 receptor activity may decrease histamine tone through the H3 autoreceptors, compounding the weight gain problem. In addition, atypical antipsychotics may affect food intake by influencing 5-HT, NA and ACh release via interactions with the H3 heteroreceptor. SN - 1878-4216 UR - https://www.unboundmedicine.com/medline/citation/19922755/The_role_of_histaminergic_H1_and_H3_receptors_in_food_intake:_a_mechanism_for_atypical_antipsychotic_induced_weight_gain L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-5846(09)00395-9 DB - PRIME DP - Unbound Medicine ER -