Vedaclidine

drugbox
IUPAC_name = (3-(3-1-butylthio)-1,2,5-thiadiazol-4-yl)-1-azabicyclo-2.2.2-octane


CAS_number = 141575-52-2
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PubChem = 60868
DrugBank =
C=13 | H=21 | N=3 | S=2
smiles = C3CC1CCN3CC1c2nsnc2SCCCC
molecular_weight = 283.455 g/mol
bioavailability =
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Vedaclidine (LY-297,802, NNC 11-1053) is a novel analgesic drug which acts as a mixed agonist-antagonist at muscarinic acetylcholine receptors, being a potent and selective agonist for the M1 and M4 subtypes, yet an antagonist at the M2, M3 and M5 subtypes. [Shannon HE, Womer DE, Bymaster FP, Calligaro DO, DeLapp NC, Mitch CH, Ward JS, Whitesitt CA, Swedberg MD, Sheardown MJ, Fink-Jensen A, Olesen PH, Rimvall K, Sauerberg P. In vivo pharmacology of butylthio [2.2.2] (LY297802 / NNC11-1053), an orally acting antinociceptive muscarinic agonist. "Life Sciences". 1997;60(13-14):969-76. PMID 9121363] [Womer DE, Shannon HE. Reversal of pertussis toxin-induced thermal allodynia by muscarinic cholinergic agonists in mice. "Neuropharmacology". 2000 Sep;39(12):2499-504. PMID 10974334] It is orally active and an effective analgesic over 3x the potency of morphine, with side effects such as salivation and tremor only occuring at many times the effective analgesic dose. [Swedberg MD, Sheardown MJ, Sauerberg P, Olesen PH, Suzdak PD, Hansen KT, Bymaster FP, Ward JS, Mitch CH, Calligaro DO, Delapp NW, Shannon HE. Butylthio [2.2.2] (NNC 11-1053/LY297802): an orally active muscarinic agonist analgesic. "Journal Pharmacology and Experimental Therapeutics". 1997 May;281(2):876-83. PMID 9152397] [Shannon HE, Sheardown MJ, Bymaster FP, Calligaro DO, Delapp NW, Gidda J, Mitch CH, Sawyer BD, Stengel PW, Ward JS, Wong DT, Olesen PH, Suzdak PD, Sauerberg P, Swedberg MD. Pharmacology of butylthio [2.2.2] (LY297802/NNC11-1053): a novel analgesic with mixed muscarinic receptor agonist and antagonist activity. "Journal of Pharmacology and Experimental Therapeutics". 1997 May;281(2):884-94. PMID 9152398] [Shannon HE, Jones CK, Li DL, Peters SC, Simmons RM, Iyengar S. Antihyperalgesic effects of the muscarinic receptor ligand vedaclidine in models involving central sensitization in rats. "Pain". 2001 Sep;93(3):221-7. PMID 11514081] Human trials showed little potential for development of dependence or abuse, [Petry NM, Bickel WK, Huddleston J, Tzanis E, Badger GJ. A comparison of subjective, psychomotor and physiological effects of a novel muscarinic analgesic, LY297802 tartrate, and oral morphine in occasional drug users. "Drug and Alcohol Dependence". 1998 Apr 1;50(2):129-36. PMID 9649964] and research is continuing into possible clinical application in the treatment of neuropathic pain and cancer pain relief. [Tata AM. Muscarinic acetylcholine receptors: new potential therapeutic targets in antinociception and in cancer therapy. "Recent Patents on CNS Drug Discovery". 2008 Jun;3(2):94-103. PMID 18537768]

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