Selective 5-HT6 Receptor Ligands (Agonist and Antagonist) Show Different Effects on Antipsychotic Drug-Induced Metabolic Dysfunctions in Rats.

Abstract

It is estimated that in patients taking antipsychotic drugs (APDs), metabolic syndrome occurs 2-3 times more often than in the general population. It manifests itself in abdominal obesity, elevated glucose concentration, and dyslipidemia. Despite the high prevalence of this disorder, only a small percentage of patients receive appropriate and effective treatment, and none of the available methods for preventing or treating APD-induced metabolic side effects is satisfactory. A promising supplement to antipsychotic therapy appears to be ligands of the serotonin 6 (5-HT6) receptor. The present study aimed to examine the chronic effects of the selected APDs (haloperidol, risperidone, olanzapine), administered alone and in combination with a selective 5-HT6 agonist (WAY-181187) or antagonist (SB-742457), on weight gain, food intake, serum lipid profile, glucose level, and a spectrum of hormones derived from adipose (leptin, adiponectin) and gastrointestinal (insulin, ghrelin) tissue in rats. SB-742457 inhibited increased weight gain and alleviated hyperglycemia induced by APDs more strongly than did WAY-181187, but also intensified dyslipidemia. WAY-181187 tended to improve the lipid profile, but increased the glucose level. The greatest benefits were obtained when WAY-181187 or SB-742457 were co-administered with haloperidol. It is difficult to assess whether the modification of the serum levels of insulin, leptin, ghrelin, and adiponectin depended on the treatment applied or other drug-independent factors; therefore, further research is needed.

• Authors: Anna Partyka, Katarzyna Górecka, Joanna Gdula-Argasińska, Natalia Wilczyńska-Zawal, Magdalena Jastrzębska-Więsek, Anna Wesołowska
• Journal: Pharmaceuticals (Basel, Switzerland) (Pharmaceuticals (Basel)) Vol. 16 Issue 2 (Jan 20 2023) ISSN: 1424-8247 [Print] Switzerland
• PMID: 37259305 (Publication Type: Journal Article)