Vedaclidine Other names (S )-3-[4-(butylthio)-1,2,5-thiadiazol-3-yl]quinuclidine ATC code
(3S )-3-[4-(Butylsulfanyl)-1,2,5-thiadiazol-3-yl]quinuclidine
CAS Number PubChem CID ChemSpider UNII ChEMBL CompTox Dashboard (EPA ) Formula C 13 H 21 N 3 S 2 Molar mass 283.45 g·mol−1 3D model (JSmol )
CCCCSC1=NSN=C1[C@@H]2CN3CCC2CC3
InChI=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
Key:WZZPXVURFDJHGI-LLVKDONJSA-N
Vedaclidine (INN ,[1] : 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.[2] [3] 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.[4] [5] [6] Human trials showed little potential for development of dependence or abuse,[7] and research is continuing into possible clinical application in the treatment of neuropathic pain and cancer pain relief.[8]
See also [ ]
References [ ]
^ "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names (Rec. INN): List 38" (PDF) . World Health Organization. 1997. Retrieved 18 November 2016 .
^ Shannon HE, Womer DE, Bymaster FP, Calligaro DO, DeLapp NC, Mitch CH, et al. (1997). "In vivo pharmacology of butylthio[2.2.2] (LY297802 / NNC11-1053), an orally acting antinociceptive muscarinic agonist". Life Sciences . 60 (13–14): 969–76. doi :10.1016/s0024-3205(97)00036-2 . PMID 9121363 .
^ Womer DE, Shannon HE (September 2000). "Reversal of pertussis toxin-induced thermal allodynia by muscarinic cholinergic agonists in mice" . Neuropharmacology . 39 (12): 2499–504. doi :10.1016/S0028-3908(00)00068-X . PMID 10974334 . S2CID 31065787 .
^ Swedberg MD, Sheardown MJ, Sauerberg P, Olesen PH, Suzdak PD, Hansen KT, et al. (May 1997). "Butylthio[2.2.2] (NNC 11-1053/LY297802): an orally active muscarinic agonist analgesic". The Journal of Pharmacology and Experimental Therapeutics . 281 (2): 876–83. PMID 9152397 .
^ Shannon HE, Sheardown MJ, Bymaster FP, Calligaro DO, Delapp NW, Gidda J, et al. (May 1997). "Pharmacology of butylthio[2.2.2] (LY297802/NNC11-1053): a novel analgesic with mixed muscarinic receptor agonist and antagonist activity". The Journal of Pharmacology and Experimental Therapeutics . 281 (2): 884–94. PMID 9152398 .
^ Shannon HE, Jones CK, Li DL, Peters SC, Simmons RM, Iyengar S (September 2001). "Antihyperalgesic effects of the muscarinic receptor ligand vedaclidine in models involving central sensitization in rats" . Pain . 93 (3): 221–7. doi :10.1016/S0304-3959(01)00319-0 . PMID 11514081 . S2CID 10256837 .
^ Petry NM, Bickel WK, Huddleston J, Tzanis E, Badger GJ (April 1998). "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 . 50 (2): 129–36. doi :10.1016/S0376-8716(98)00026-X . PMID 9649964 .
^ Tata AM (June 2008). "Muscarinic acetylcholine receptors: new potential therapeutic targets in antinociception and in cancer therapy". Recent Patents on CNS Drug Discovery . 3 (2): 94–103. doi :10.2174/157488908784534621 . PMID 18537768 .
Analgesics (N02A , N02B )
Opioids
Opiates /opium
Codeine #
Morphine # (+naltrexone )
Opium
Laudanum
Paregoric
Semisynthetic Synthetic
Paracetamol -typeNSAIDs
Propionates Oxicams
Isoxicam
Lornoxicam
Meloxicam
Piroxicam
Tenoxicam
Acetates COX-2 inhibitors Fenamates Salicylates Pyrazolones
Aminophenazone ‡
Ampyrone
Metamizole (dipyrone)
Nifenazone
Phenazone
Propyphenazone (+paracetamol/caffeine )
Others
Cannabinoids
Cannabidiol
Cannabis
Nabilone
Nabiximols
Tetrahydrocannabinol (dronabinol)
Ion channel modulators
Calcium blockers
Alcohol (ethanol)
Gabapentin
Gabapentin enacarbil
Leconotide
Mirogabalin
Pregabalin
Ziconotide
Sodium blockers
Carbamazepine
Lacosamide
Local anesthetics (e.g., cocaine , lidocaine )
Mexiletine
Nefopam
Tricyclic antidepressants (e.g., amitriptyline # )
Nav 1.7/1.8-selective: DSP-2230 §
Funapide §
PF-05089771 §
Potassium openers
Myorelaxants
Carisoprodol
Chlorzoxazone
Cyclobenzaprine
Mephenoxalone
Methocarbamol
Orphenadrine
Others
# WHO-EM
‡ Withdrawn from market
Clinical trials :
† Phase III
§ Never to phase III
mAChRs
Agonists Antagonists
3-Quinuclidinyl benzilate
4-DAMP
Aclidinium bromide (+formoterol )
Abediterol
AF-DX 384
Ambutonium bromide
Anisodamine
Anisodine
Antihistamines (first-generation) (e.g., brompheniramine , buclizine , captodiame , chlorphenamine (chlorpheniramine) , cinnarizine , clemastine , cyproheptadine , dimenhydrinate , dimetindene , diphenhydramine , doxylamine , meclizine , mequitazine , perlapine , phenindamine , pheniramine , phenyltoloxamine , promethazine , propiomazine , triprolidine )
Atropine
Atropine methonitrate
Atypical antipsychotics (e.g., clozapine , fluperlapine , olanzapine (+fluoxetine ), , quetiapine , tenilapine , zotepine )
Benactyzine
Benzatropine (benztropine)
Benzilone
Benzilylcholine mustard
Benzydamine
Biperiden
Bornaprine
Camylofin
CAR-226,086
CAR-301,060
CAR-302,196
CAR-302,282
CAR-302,668
Caramiphen
Cimetropium bromide
Clidinium bromide
Cloperastine
CS-27349
Cyclobenzaprine
Cyclopentolate
Darifenacin
Desfesoterodine
Dexetimide
Dicycloverine (dicyclomine)
Dihexyverine
Difemerine
Diphemanil metilsulfate
Ditran
Drofenine
EA-3167
EA-3443
EA-3580
EA-3834
Emepronium bromide
Etanautine
Etybenzatropine (ethybenztropine)
Fenpiverinium
Fentonium bromide
Fesoterodine
Flavoxate
Glycopyrronium bromide (+beclometasone/formoterol , +indacaterol )
Hexocyclium
Himbacine
Homatropine
Imidafenacin
Ipratropium bromide (+salbutamol )
Isopropamide
Hyoscyamine
Mamba toxin 3
Mamba toxin 7
Mazaticol
Mebeverine
Meladrazine
Mepenzolate
Methantheline
Methoctramine
Methylatropine
Methylhomatropine
Methylscopolamine
Metixene
Muscarinic toxin 7
N-Ethyl-3-piperidyl benzilate
N-Methyl-3-piperidyl benzilate
Nefopam
Octatropine methylbromide (anisotropine methylbromide)
Orphenadrine
Otenzepad (AF-DX 116)
Otilonium bromide
Oxapium iodide
Oxitropium bromide
Oxybutynin
Oxyphencyclimine
Oxyphenonium bromide
PD-102,807
PD-0298029
Penthienate
Pethidine
Phenglutarimide
Phenyltoloxamine
Pipenzolate bromide
Piperidolate
Pirenzepine
Piroheptine
Pizotifen
Poldine
Pridinol
Prifinium bromide
Procyclidine
Profenamine (ethopropazine)
Propantheline bromide
Propiverine
Quinidine
3-Quinuclidinyl thiochromane-4-carboxylate
Revefenacin
Rociverine
Scopolamine (hyoscine)
Scopolamine butylbromide (hyoscine butylbromide)
Sofpironium bromide
Solifenacin
SSRIs (e.g., femoxetine , paroxetine )
Telenzepine
Terodiline
Tetracyclic antidepressants (e.g., amoxapine , maprotiline , mianserin , mirtazapine )
Tiemonium iodide
Timepidium bromide
Tiotropium bromide
Tofenacin
Tolterodine
Tricyclic antidepressants (e.g., amitriptyline (+perphenazine ), amitriptylinoxide , butriptyline , cidoxepin , clomipramine , desipramine , , dibenzepin , dosulepin (dothiepin) , doxepin , imipramine , lofepramine , nitroxazepine , northiaden (desmethyldosulepin) , nortriptyline , protriptyline , quinupramine , trimipramine )
Tridihexethyl
Trihexyphenidyl
Trimebutine
Tropatepine
Tropicamide
Trospium chloride
Typical antipsychotics (e.g., chlorpromazine , chlorprothixene , cyamemazine (cyamepromazine) , loxapine , mesoridazine , thioridazine )
Umeclidinium bromide (+vilanterol )
WIN-2299
Xanomeline
Precursors (and prodrugs )
Acetyl-coA
Adafenoxate
Choline (lecithin )
Citicoline
Cyprodenate
Dimethylethanolamine
Glycerophosphocholine
Meclofenoxate (centrophenoxine)
Phosphatidylcholine
Phosphatidylethanolamine
Phosphorylcholine
Pirisudanol
See also: Receptor/signaling modulators • Nicotinic acetylcholine receptor modulators • Acetylcholine metabolism/transport modulators