SB-205384

SB-205384

Legal status
Legal status	US: Investigational New Drug
Identifiers
IUPAC name But-2-ynyl 4-amino-7-hydroxy-2-methyl-5,6,7,8-tetrahydro-[1]benzothiolo[3,2-e]pyridine-3-carboxylate
CAS Number	160296-13-9  Y
PubChem CID	197690
ChemSpider	171116  N
CompTox Dashboard (EPA)	DTXSID00936259
Chemical and physical data
Formula	C17H18N2O3S
Molar mass	330.40 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC#CCOC(=O)c1c(C)nc2sc3CC(O)CCc3c2c1N
InChI InChI=1S/C17H18N2O3S/c1-3-4-7-22-17(21)13-9(2)19-16-14(15(13)18)11-6-5-10(20)8-12(11)23-16/h10,20H,5-8H2,1-2H3,(H2,18,19) N Key:JDTZAGLGBRRCJT-UHFFFAOYSA-N N
NY  (what is this?)    (verify)

SB-205384 is an anxiolytic drug. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic.

SB-205384 is a GABA_A positive allosteric modulator, which binds preferentially to α3, α5, and α6 subunit containing subtypes. ^{[1] [2]} It has a novel mechanism of action, prolonging the duration of GABA-mediated chloride flux but without increasing the intensity of the response, and this may give it an unusual pharmacological profile, ^[3] with tests showing that it alters the firing of some populations of neurons while leaving others unaffected. ^[4] Animal studies have shown it to produce both anxiolytic and anti-aggressive effects, but with little sedation or other behavioural changes. ^{[5] [6]}

References

1. Heidelberg LS, Warren JW, Fisher JL (October 2013). "SB-205384 is a positive allosteric modulator of recombinant GABAA receptors containing rat α3, α5, or α6 subunit subtypes coexpressed with β3 and γ2 subunits". The Journal of Pharmacology and Experimental Therapeutics. 347 (1): 235–41. doi:10.1124/jpet.113.207324. PMC   3781410 . PMID   23902941.
2. Meadows HJ, Kumar CS, Pritchett DB, Blackburn TP, Benham CD (March 1998). "SB-205384: a GABA(A) receptor modulator with novel mechanism of action that shows subunit selectivity". British Journal of Pharmacology. 123 (6): 1253–9. doi:10.1038/sj.bjp.0701721. PMC   1565273 . PMID   9559912.
3. Meadows HJ, Harries MH, Thompson M, Benham CD (August 1997). "Effect of SB-205384 on the decay of GABA-activated chloride currents in granule cells cultured from rat cerebellum". British Journal of Pharmacology. 121 (7): 1334–8. doi:10.1038/sj.bjp.0701251. PMC   1564816 . PMID   9257911.
4. Ing T, Poulter MO (February 2007). "Diversity of GABA(A) receptor synaptic currents on individual pyramidal cortical neurons". The European Journal of Neuroscience. 25 (3): 723–34. doi:10.1111/j.1460-9568.2007.05331.x. PMID   17313570. S2CID   9361003.
5. Navarro JF, Burón E, Martín-López M (February 2006). "Anxiolytic-like activity of SB-205384 in the elevated plus-maze test in mice". Psicothema. 18 (1): 100–4. PMID   17296016.
6. Navarro JF, Burón E, Martín-López M (February 2008). "Effects of SB-205384, a positive modulator of alpha3-subunit-containing GABA-A receptors, on isolation-induced aggression in male mice". Psicothema. 20 (1): 144–7. PMID   18206077.