vedaclidine

{{Short description|Chemical compound}}

{{Drugbox

| IUPAC_name = (3S)-3-[4-(Butylsulfanyl)-1,2,5-thiadiazol-3-yl]quinuclidine

| image = Vedaclidine.svg

| width = 175

| image2 = Vedaclidine 3D.png

| width2 = 120

| tradename =

| pregnancy_category =

| legal_status =

| routes_of_administration = oral

| bioavailability =

| metabolism =

| elimination_half-life =

| excretion =

| CAS_number = 141575-50-0

| ATC_prefix = None

| ATC_suffix =

| PubChem = 9889093

| ChemSpiderID = 8064764

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 98IW5HAV1N

| ChEMBL = 136807

| C=13 | H=21 | N=3 | S=2

| SMILES = CCCCSC1=NSN=C1[C@@H]2CN3CCC2CC3

| StdInChI = 1S/C13H21N3S2/c1-2-3-8-17-13-12(14-18-15-13)11-9-16-6-4-10(11)5-7-16/h10-11H,2-9H2,1H3/t11-/m1/s1

| StdInChIKey = WZZPXVURFDJHGI-LLVKDONJSA-N

| synonyms = (S)-3-[4-(butylthio)-1,2,5-thiadiazol-3-yl]quinuclidine

}}

Vedaclidine (INN,{{cite web | title = International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names (Rec. INN): List 38 | url =https://www.who.int/medicines/publications/druginformation/innlists/RL38.pdf | publisher = World Health Organization | access-date = 18 November 2016 | date = 1997}}{{rp|180}} codenamed LY-297,802, NNC 11-1053) is an experimental 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.{{cite journal | vauthors = 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 | display-authors = 6 | title = In vivo pharmacology of butylthio[2.2.2] (LY297802 / NNC11-1053), an orally acting antinociceptive muscarinic agonist | journal = Life Sciences | volume = 60 | issue = 13–14 | pages = 969–76 | year = 1997 | pmid = 9121363 | doi = 10.1016/s0024-3205(97)00036-2 }}{{cite journal | vauthors = Womer DE, Shannon HE | title = Reversal of pertussis toxin-induced thermal allodynia by muscarinic cholinergic agonists in mice | journal = Neuropharmacology | volume = 39 | issue = 12 | pages = 2499–504 | date = September 2000 | pmid = 10974334 | doi = 10.1016/S0028-3908(00)00068-X | s2cid = 31065787 }} It is orally active and an effective analgesic over 3× the potency of morphine, with side effects such as salivation and tremor only occurring at many times the effective analgesic dose.{{cite journal | vauthors = Swedberg MD, Sheardown MJ, Sauerberg P, Olesen PH, Suzdak PD, Hansen KT, Bymaster FP, Ward JS, Mitch CH, Calligaro DO, Delapp NW, Shannon HE | display-authors = 6 | title = Butylthio[2.2.2] (NNC 11-1053/LY297802): an orally active muscarinic agonist analgesic | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 281 | issue = 2 | pages = 876–83 | date = May 1997 | pmid = 9152397 }}{{cite journal | vauthors = 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 | display-authors = 6 | title = Pharmacology of butylthio[2.2.2] (LY297802/NNC11-1053): a novel analgesic with mixed muscarinic receptor agonist and antagonist activity | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 281 | issue = 2 | pages = 884–94 | date = May 1997 | pmid = 9152398 }}{{cite journal | vauthors = Shannon HE, Jones CK, Li DL, Peters SC, Simmons RM, Iyengar S | title = Antihyperalgesic effects of the muscarinic receptor ligand vedaclidine in models involving central sensitization in rats | journal = Pain | volume = 93 | issue = 3 | pages = 221–7 | date = September 2001 | pmid = 11514081 | doi = 10.1016/S0304-3959(01)00319-0 | s2cid = 10256837 }} Human trials showed little potential for development of dependence or abuse,{{cite journal | vauthors = Petry NM, Bickel WK, Huddleston J, Tzanis E, Badger GJ | title = A comparison of subjective, psychomotor and physiological effects of a novel muscarinic analgesic, LY297802 tartrate, and oral morphine in occasional drug users | journal = Drug and Alcohol Dependence | volume = 50 | issue = 2 | pages = 129–36 | date = April 1998 | pmid = 9649964 | doi = 10.1016/S0376-8716(98)00026-X }} and research is continuing into possible clinical application in the treatment of neuropathic pain and cancer pain relief.{{cite journal | vauthors = Tata AM | title = Muscarinic acetylcholine receptors: new potential therapeutic targets in antinociception and in cancer therapy | journal = Recent Patents on CNS Drug Discovery | volume = 3 | issue = 2 | pages = 94–103 | date = June 2008 | pmid = 18537768 | doi = 10.2174/157488908784534621 }}