Neuropharmacologic studies on the brain serotonin1A receptor using the selective agonist osemozotan.

Abstract

Alterations in serotonin (5-HT) neurochemistry have been implicated in the etiology of major neuropsychiatric disorders such as anxiety-spectrum disorders, depression, and schizophrenia. The neuromodulatory effects of 5-HT are mediated through 14 receptor subtypes, and those receptors, including the 5-HT1A receptor, are considered to be potential targets for the treatment of psychiatric disorders. We developed the novel 5-HT1A receptor agonist MKC-242 (called osemozotan) and characterized its neurochemical and pharmacological profiles. 5-HT1A receptor agonists modulate the release of amine neurotransmitters through the activation of presynaptic or postsynaptic 5-HT1A receptors in the brain. The agonist has antianxiety and antidepressant effects and improves abnormal behaviors such as aggressive behavior and deficits of prepulse inhibition in isolation-reared mice. We also demonstrated that spinal 5-HT1A receptor activation is involved in isolation rearing-induced hypoalgesia. Concerning the mechanism for induction of isolation-induced abnormal behaviors, we have recently found that the raphe-prefrontal 5-HT system plays a key role in encounter stimulation-induced hyperactivity in isolation-reared mice. Furthermore, we showed that osemozotan attenuates psychostimulant-induced behavioral sensitization and that prefrontal dopamine release is enhanced by functional interaction between the 5-HT1A receptor and other receptors. This review summarizes the neuropharmacology of the 5-HT1A receptor, focusing on our studies using osemozotan, and suggests that the 5-HT1A receptor may be a target molecule for the treatment of psychiatric disorders, pain, and drug dependence.

• Authors: Toshio Matsuda
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 36 Issue 12 Pg. 1871-82 ( 2013) ISSN: 1347-5215 [Electronic] Japan
• PMID: 24292048 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Dioxanes
• Dioxoles
• Serotonin 5-HT1 Receptor Agonists
• Receptor, Serotonin, 5-HT1A
• osemozotan
• Dopamine

Topics

• Animals
• Dioxanes (pharmacology)
• Dioxoles (pharmacology)
• Dopamine
• Humans
• Prefrontal Cortex (metabolism)
• Receptor, Serotonin, 5-HT1A (metabolism)
• Serotonin 5-HT1 Receptor Agonists (pharmacology)