Reducing olanzapine-induced weight gain side effect by using betahistine: a study in the rat model.
Olanzapine is effective at treating multiple domains of schizophrenia symptoms. However, it induces serious metabolic side effects. Antipsychotic drug's antagonistic affinity to histamine H₁ receptors has been identified as a main contributor for weight gain/obesity side effects. This study therefore investigated whether a combined treatment of betahistine (a H₁ receptor agonist and H₃ receptor antagonist) could reduce the body weight/obesity induced by olanzapine. Female Sprague Dawley rats were treated orally with olanzapine (1 mg/kg, t.i.d.) and/or betahistine (2.67 mg/kg, t.i.d.), or vehicle for two weeks. Rats treated with olanzapine exhibited significant body weight gain and increased food intake. Co-treatment of olanzapine with betahistine significantly prevented (-45%) weight gain and reduced feeding efficiency compared to sole olanzapine treatment. Betahistine treatment alone had no effect on weight gain and food intake. Olanzapine reduced locomotor activity, but not betahistine. These findings demonstrate that olanzapine-induced body weight gain can partially be reduced by co-treatment with betahistine. Betahistine has H₃ receptor antagonistic effects to increase histamine release, which may augment its direct agonistic effects on H₁ receptors. These findings have important implications for clinical trials using betahistine to control antipsychotic-induced obesity side effects.
Centre for Translational Neuroscience, School of Health Sciences, University of Wollongong, Wollongong, NSW, Australia. chao@uow.edu.au
Chao
C
Deng
Jiamei
J
Lian
Nagesh
N
Pai
Xu-Feng
XF
Huang
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001067:Appetite Depressants / Q000009:adverse effects / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000009:adverse effects*; D001621:Betahistine / Q000009:adverse effects / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D017442:Histamine Agonists / Q000009:adverse effects / Q000627:therapeutic use; D054828:Histamine H3 Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D006963:Hyperphagia / Q000139:chemically induced / Q000517:prevention & control*; D009043:Motor Activity / Q000187:drug effects; D000077152:Olanzapine; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011969:Receptors, Histamine H1 / Q000737:chemistry; D015430:Weight Gain / Q000187:drug effects*
D014150:Antipsychotic Agents; D001067:Appetite Depressants; D017442:Histamine Agonists; D054828:Histamine H3 Antagonists; D011969:Receptors, Histamine H1; D001569:Benzodiazepines; D000077152:Olanzapine; D001621:Betahistine