Abstract | BACKGROUND: METHODS: Non-clinical studies were conducted to assess the metabolic effects of olanzapine and samidorphan alone and in combination at clinically relevant exposure levels. RESULTS: Chronic olanzapine administration in male and female rats shifted body composition by increasing adipose mass, which was accompanied by an increase in the rate of weight gain in female rats. Co-administration of samidorphan normalized body composition in both sexes and attenuated weight gain in female rats. In hyperinsulinemic euglycemic clamp experiments conducted prior to measurable changes in weight and/or body composition, olanzapine decreased hepatic insulin sensitivity and glucose uptake in muscle while increasing uptake in adipose tissue. Samidorphan appeared to normalize glucose utilization in both tissues, but did not restore hepatic insulin sensitivity. In subsequent studies, samidorphan normalized olanzapine-induced decreases in whole-body glucose clearance following bolus insulin administration. Results from experiments in female monkeys paralleled the effects in rats. CONCLUSIONS:
|
Authors | Jacobi I Cunningham, David J Eyerman, Mark S Todtenkopf, Reginald L Dean, Daniel R Deaver, Connie Sanchez, Mark Namchuk |
Journal | Journal of psychopharmacology (Oxford, England)
(J Psychopharmacol)
Vol. 33
Issue 10
Pg. 1303-1316
(10 2019)
ISSN: 1461-7285 [Electronic] United States |
PMID | 31294646
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antipsychotic Agents
- Drug Combinations
- Narcotic Antagonists
- Naltrexone
- 3-carboxamido-4-hydroxynaltrexone
- Olanzapine
|
Topics |
- Adipose Tissue
(drug effects)
- Animals
- Antipsychotic Agents
(adverse effects)
- Drug Combinations
- Female
- Glucose Metabolism Disorders
(chemically induced, drug therapy, prevention & control)
- Macaca fascicularis
- Male
- Naltrexone
(administration & dosage, analogs & derivatives, pharmacology)
- Narcotic Antagonists
(administration & dosage, pharmacology)
- Olanzapine
(adverse effects)
- Rats
- Rats, Sprague-Dawley
- Sex Factors
- Weight Gain
(drug effects)
|