Skip to main content

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

Journal Article


Download full-text (Open Access)

Abstract


  • Atypical antipsychotics such as olanzapine and clozapine are effective at treating the multiple domains of

    schizophrenia, with a lowrisk of extra-pyramidal side-effects. However amajor downfall to their use is metabolicside-effects particularly weight gain/obesity,which occurs by unknownmechanisms. The present paper explores the potential candidature of histaminergic neurotransmission in the mechanisms of atypical antipsychoticinduced weight gain, with a focus on the histaminergic H1 and H3 receptors. Olanzapine and clozapine have a high affinity for the H1 receptor, andmeta-analyses showa strong correlation between risk ofweight gain andH1 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, boththrough its control of histamine and its influence onother 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 theweight gain problem. In addition, atypical antipsychoticsmay affect food intake by influencing 5-HT, NA and ACh release via interactions with the H3 heteroreceptor.

Publication Date


  • 2010

Citation


  • Deng, C., Weston-Green, K. & Huang, X. (2010). The role of histaminergic H1 and H3 receptors in food intake:-A mechanism fo atypical antipsychotic-induced weight gain?. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 34 (1), 1-4.

Scopus Eid


  • 2-s2.0-73649134285

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=4461&context=hbspapers

Ro Metadata Url


  • http://ro.uow.edu.au/hbspapers/3409/

Has Global Citation Frequency


Number Of Pages


  • 3

Start Page


  • 1

End Page


  • 4

Volume


  • 34

Issue


  • 1

Place Of Publication


  • United States

Abstract


  • Atypical antipsychotics such as olanzapine and clozapine are effective at treating the multiple domains of

    schizophrenia, with a lowrisk of extra-pyramidal side-effects. However amajor downfall to their use is metabolicside-effects particularly weight gain/obesity,which occurs by unknownmechanisms. The present paper explores the potential candidature of histaminergic neurotransmission in the mechanisms of atypical antipsychoticinduced weight gain, with a focus on the histaminergic H1 and H3 receptors. Olanzapine and clozapine have a high affinity for the H1 receptor, andmeta-analyses showa strong correlation between risk ofweight gain andH1 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, boththrough its control of histamine and its influence onother 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 theweight gain problem. In addition, atypical antipsychoticsmay affect food intake by influencing 5-HT, NA and ACh release via interactions with the H3 heteroreceptor.

Publication Date


  • 2010

Citation


  • Deng, C., Weston-Green, K. & Huang, X. (2010). The role of histaminergic H1 and H3 receptors in food intake:-A mechanism fo atypical antipsychotic-induced weight gain?. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 34 (1), 1-4.

Scopus Eid


  • 2-s2.0-73649134285

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=4461&context=hbspapers

Ro Metadata Url


  • http://ro.uow.edu.au/hbspapers/3409/

Has Global Citation Frequency


Number Of Pages


  • 3

Start Page


  • 1

End Page


  • 4

Volume


  • 34

Issue


  • 1

Place Of Publication


  • United States