CGS-20625 explained

CGS-20625 is an anxiolytic drug used in scientific research. It has similar effects to benzodiazepine drugs,^[1] but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic.^{[2] [3]} It produces anxiolytic and anticonvulsant effects, but with no sedative effects even at high doses, and no significant muscle relaxant effects.^[4] It is orally active in humans, but with relatively low bioavailability.^[5]

CGS-20625 is a positive allosteric modulator at several GABA_A receptors types. Due to its alicyclic moiety potency at γ1 subunit, containing receptor types is more pronounced for CGS-20625 compared to benzodiazepines.^[1] γ1 subunits are expressed at higher levels in the central amygdala.^[6]

Notes and References

1. Khom S, Baburin I, Timin EN, Hohaus A, Sieghart W, Hering S . 15082432 . Pharmacological properties of GABAA receptors containing gamma1 subunits . Mol. Pharmacol. . 69 . 2 . 640–9 . Feb 2006 . 16272224 . 10.1124/mol.105.017236 .
2. Bennett DA . Pharmacology of the pyrazolo-type compounds: agonist, antagonist and inverse agonist actions . Physiol. Behav. . 41 . 3 . 241–5 . 1987 . 2893398 . 10.1016/0031-9384(87)90360-X. 45892825 .
3. Brunner LA, Luders RC . Determination of a potential anxiolytic drug (CGS 20625) in human plasma by high-performance liquid chromatography . J. Chromatogr. . 568 . 2 . 487–93 . Aug 1991 . 1686029 . 10.1016/0378-4347(91)80188-I .
4. Williams M, Bennett DA, Loo PS . CGS 20625, a novel pyrazolopyridine anxiolytic . J Pharmacol Exp Ther . 248 . 1 . 89–96 . Jan 1989 . 2563294 . etal.
5. Hirschberg Y, Oberle RL, Ortiz M, Lau H, Markowska M . Oral absorption of CGS-20625, an insoluble drug, in dogs and man . J Pharmacokinet Biopharm . 23 . 1 . 11–23 . Feb 1995 . 8576841 . 10.1007/BF02353783 . 22126140 .
6. Esmaeili A, Lynch JW, Sah P . 1590604 . GABAA receptors containing gamma1 subunits contribute to inhibitory transmission in the central amygdala . J. Neurophysiol. . 101 . 1 . 341–9 . January 2009 . 19004994 . 10.1152/jn.90991.2008 .