The dosage-dependent effects of cevimeline in preventing olanzapine-induced metabolic side-effects in female rats.

Abstract

Olanzapine has been used for the treatment of schizophrenia and other mental disorders. However, it is associated with serious weight gain and other metabolic side-effects. The antagonistic affinity of olanzapine to muscarinic M3 receptors has been evidenced as one of the main contributors for its weight gain and other metabolic side-effects. Therefore, this study investigated whether the co-treatment of cevimeline (a M3 receptor agonist) could prevent the metabolic side-effects associated with olanzapine medication. Female Sprague Dawley rats were treated orally with olanzapine (2 mg/kg, t.i.d.) and/or cevimeline at 3 dosages (3, 6, 9 mg/kg, t.i.d.), or vehicle for two weeks. Weight gain and food/water intake were measured throughout the drug treatment period. Intraperitoneal glucose tolerance tests and open field tests were conducted. Olanzapine-treated rats demonstrated significantly elevated body weight gain, food intake, feeding efficiency, total white fat mass, liver mass, and plasma triglyceride levels, which could be partly reversed by the co-treatment with cevimeline in a dosage-dependent manner. In general, the body weight gain can only be reversed by the co-treatment of 9 mg/kg cevimeline. The cevimeline co-treatment decreased plasma triglyceride and glucose levels compared with olanzapine only treatment. The results suggested a dosage-dependent effect of cevimeline in ameliorating olanzapine-induced weight gain and metabolic side-effects, which supports further clinical trials using cevimeline to control weight gain and metabolic side-effects caused by antipsychotic medications.

• Authors: Jiamei Lian, Chao Deng
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 191 Pg. 172878 (04 2020) ISSN: 1873-5177 [Electronic] United States
• PMID: 32112786 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Blood Glucose
• Quinuclidines
• Receptor, Muscarinic M3
• Thiophenes
• Triglycerides
• cevimeline
• Olanzapine

Topics

• Adipose Tissue (drug effects)
• Adiposity (drug effects)
• Animals
• Behavior, Animal (drug effects)
• Blood Glucose (drug effects)
• Dose-Response Relationship, Drug
• Drug Interactions
• Eating (drug effects)
• Female
• Locomotion (drug effects)
• Metabolic Syndrome (blood, chemically induced, prevention & control)
• Olanzapine (adverse effects, pharmacology)
• Open Field Test
• Quinuclidines (administration & dosage, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptor, Muscarinic M3 (agonists, antagonists & inhibitors)
• Thiophenes (administration & dosage, pharmacology)
• Treatment Outcome
• Triglycerides (blood)
• Weight Gain (drug effects)