This article may be too technical for most readers to understand.(January 2023) |
Saclofen is a competitive antagonist for the GABAB receptor.[1] This drug is an analogue of the GABAB agonist baclofen. The GABAB receptor is heptahelical receptor, expressed as an obligate heterodimer, which couples to the Gi/o class of heterotrimeric G-proteins. The action of saclofen on the central nervous system is understandably modest, because G-proteins rely on an enzyme cascade to alter cell behavior while ionotropic receptors immediately change the ionic permeability of the neuronal plasma membrane, thus changing its firing patterns. These particular receptors, presynaptically inhibit N- and P/Q- voltage-gated calcium channels (VGCCs) via a direct interaction of the dissociated beta gamma subunit of the g-protein with the intracellular loop between the 1st and 2nd domain of the VGCC's alpha-subunit; postsynaptically, these potentiate Kir currents. Both result in inhibitory effects.
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IUPAC name
3-Amino-2-(4-chlorophenyl)propane-1-sulfonic acid
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Identifiers | |
3D model (JSmol)
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ChEBI | |
ChemSpider | |
PubChem CID
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UNII | |
CompTox Dashboard (EPA)
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Properties | |
C9H12ClNO3S | |
Molar mass | 249.71 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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However, in animal experiments, saclofen is paradoxically observed to have an antiepileptic effect. This is probably because GABAB effect is coupled to excitation in the thalamo-cortical circuits — Kir coupling via G
Saclofen has two enantiomeric forms. The (R)-stereoisomer is the one that binds to the GABAB receptor, whereas the (S)-stereoisomer does not.[2]
References
edit- ^ Rang, HP; MM Dale; JM Ritter; RJ Flower (2007). Rang and Dale's Pharmacology (6th ed.). Churchill Livingstone Elsevier. ISBN 978-0-443-06911-6.
- ^ Kerr, D. I. B; Ong, J.; Vaccher, C.; Berthelot, P.; Flouquet, N.; Vaccher, M.-P.; Debaert, M. (1996). "GABAB receptor antagonism by resolved (R)-saclofen in the guinea-pig ileum". European Journal of Pharmacology. 308 (3): R1–R2. doi:10.1016/0014-2999(96)00334-2. PMID 8858312.