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RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist
D W Bonhaus1, K K Weinhardt, M Taylor
1Institute of Pharmacology, Roche Bioscience, Palo Alto, CA 94304, USA.
Neuropharmacology
|April 1, 1997
Summary
Researchers developed RS-102221, the first selective 5-HT2C receptor antagonist. This high-affinity compound shows potential for exploring serotonin receptor functions and related physiological effects.
Area of Science:
- Pharmacology
- Neuroscience
- Receptor Biology
Background:
- The 5-HT2C receptor is a key subtype within the 5-HT2 receptor family.
- Selective antagonists for 5-HT2A and 5-HT2B receptors exist, but a 5-HT2C selective antagonist was previously undisclosed.
Purpose of the Study:
- To develop and characterize a selective antagonist for the 5-HT2C receptor.
- To investigate the functional role of 5-HT2C receptors in physiological processes.
Main Methods:
- Synthesis and characterization of RS-102221, a novel benzenesulfonamide derivative.
- Affinity and selectivity assays using human and rat 5-HT2C receptors compared to 5-HT2A and 5-HT2B receptors.
- Functional antagonism assessment via cell-based microphysiometry and in vivo rodent models.
Main Results:
- RS-102221 demonstrated nanomolar affinity for human (pKi = 8.4) and rat (pKi = 8.5) 5-HT2C receptors.
- The compound exhibited over 100-fold selectivity for 5-HT2C over 5-HT2A and 5-HT2B receptors.
- In vivo, RS-102221 administration increased food intake and weight gain in rats, consistent with 5-HT2C antagonism.
Conclusions:
- RS-102221 is identified as the first highly selective and potent 5-HT2C receptor antagonist.
- This novel compound provides a valuable tool for further research into 5-HT2C receptor pharmacology and function.