Hypothermic, ACTH, and cortisol responses to ipsapirone in patients with mania and healthy controls

• Published in: Journal of affective disorders 1999-08, Vol.54 (3), p.295-301
• Main Authors: Yatham, Lakshmi N, Shiah, I-Shin, Lam, Raymond W, Tam, Edwin M, Zis, Athanasios P
• Format: Article
• Language: English
• Subjects: 5-HT 1A receptors; ACTH; Administration, Oral; Adrenocorticotropic Hormone - drug effects; Adrenocorticotropic Hormone - metabolism; Adult; Adult and adolescent clinical studies; Biological and medical sciences; Bipolar Disorder - drug therapy; Cortisol; Female; Humans; Hydrocortisone - metabolism; Hypothermia; Ipsapirone; Male; Mania; Medical sciences; Middle Aged; Mood disorders; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Pyrimidines - pharmacology; Receptors, Serotonin - drug effects; Receptors, Serotonin - physiology; Serotonin; Serotonin Receptor Agonists - pharmacology
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/S0165-0327(98)00186-4

Background: The selective 5-HT 1A receptor agonist ipsapirone causes dose-dependent decrease in body temperature and increase in adrenocorticotropic hormone (ACTH) and cortisol release in humans. These responses are attenuated by 5-HT 1A receptor antagonists, suggesting that hypothermia, ACTH and cortisol release induced by ipsapirone are indeed mediated by 5-HT 1A receptors and that these responses provide a valid index of 5-HT 1A receptor function in humans. Methods: To examine the 5-HT 1A receptor sensitivity in patients with mania, we studied six manic patients and six age and sex matched healthy controls. After obtaining a blood sample for baseline hormone levels and measuring body temperature, a single dose of 0.3 mg/kg of ipsapirone was given orally to all the subjects and further bloods and temperature reading were obtained every 30 minutes for 3 hours. Results: We found that ACTH and cortisol responses to ipsapirone were significantly increased in mania when compared to healthy controls, but there was no significant difference in hypothermic response to ipsapirone between the two groups. Limitations: A lack of placebo control, heterogeneity of patients, and a small sample size are the limitations. Conclusions: Our findings suggest that manic patients may have enhanced postsynaptic 5-HT 1A receptor sensitivity, but presynaptic 5-HT 1A receptors are unaltered in this condition. Further placebo-controlled studies with a larger number of manic patients are needed to verify this.