Target Information

Target General Infomation
Target ID
T09130
Former ID
TTDI01749
Target Name
Muscarinic receptor
Target Type
Successful
Disease Alzheimer disease [ICD9: 331; ICD10: G30]
Amnesia [ICD10: F04]
Asthma [ICD10: J45]
Allergic rhinitis [ICD9: 472.0, 477, 995.3; ICD10: J00, J30, J31.0, T78.4]
Cognitive disorders [ICD9: 290-294, 294.0, 780.09, 780.9, 780.93; ICD10: F01-F07, F04, F05, R41.3]
Chronic obstructive pulmonary disease [ICD9: 490-492, 494-496; ICD10: J40-J44, J47]
Overactive bladder disorder [ICD9: 188, 596.51; ICD10: C67, N32.81]
Urinary incontinence [ICD9: 788.3; ICD10: N39.3, N39.4, R32]
Xerostomia [ICD9: 527.7; ICD10: K11.7, R68.2]
Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through theaction of G proteins. Primary transducing effect is Pi turnover.
BioChemical Class
GPCR rhodopsin
Sequence
MTLHNNSTTSPLFPNISSSWIHSPSDAGLPPGTVTHFGSYNVSRAAGNFSSPDGTTDDPL
GGHTVWQVVFIAFLTGILALVTIIGNILVIVSFKVNKQLKTVNNYFLLSLACADLIIGVI
SMNLFTTYIIMNRWALGNLACDLWLAIDYVASNASVMNLLVISFDRYFSITRPLTYRAKR
TTKRAGVMIGLAWVISFVLWAPAILFWQYFVGKRTVPPGECFIQFLSEPTITFGTAIAAF
YMPVTIMTILYWRIYKETEKRTKELAGLQASGTEAETENFVHPTGSSRSCSSYELQQQSM
KRSNRRKYGRCHFWFTTKSWKPSSEQMDQDHSSSDSWNNNDAAASLENSASSDEEDIGSE
TRAIYSIVLKLPGHSTILNSTKLPSSDNLQVPEEELGMVDLERKADKLQAQKSVDDGGSF
PKSFSKLPIQLESAVDTAKTSDVNSSVGKSTATLPLSFKEATLAKRFALKTRSQITKRKR
MSLVKEKKAAQTLSAILLAFIITWTPYNIMVLVNTFCDSCIPKTFWNLGYWLCYINSTVN
PVCYALCNKTFRTTFKMLLLCQCDKKKRRKQQYQQRQSVIFHKRAPEQAL
Drugs and Mode of Action
Drug(s) Incruse Ellipta Drug Info Approved Chronic obstructive pulmonary disease [551871]
Isopropamide iodide Drug Info Approved Allergic rhinitis [551871]
Oxybutynin hydrochloride Drug Info Approved Urinary incontinence [551871]
Seebri Drug Info Approved Chronic obstructive pulmonary disease [524819], [551969]
SUN-101 Drug Info Phase 3 Chronic obstructive pulmonary disease [524970]
TD-4208 Drug Info Phase 3 Chronic obstructive pulmonary disease [525280]
THVD-201 Drug Info Phase 3 Overactive bladder disorder [525249]
APD-515 Drug Info Phase 2 Xerostomia [549205]
AZD-2115 Drug Info Phase 2 Chronic obstructive pulmonary disease [524708]
AZD-8683 Drug Info Phase 2 Chronic obstructive pulmonary disease [524096]
AZD-9164 Drug Info Phase 2 Chronic obstructive pulmonary disease [522724]
EP-101 Drug Info Phase 2 Chronic obstructive pulmonary disease [523605]
QAX-028 Drug Info Phase 2 Chronic obstructive pulmonary disease [522951]
SMP-986 Drug Info Phase 2 Overactive bladder disorder [548182]
PUR0200 Drug Info Phase 1 Chronic obstructive pulmonary disease [524396]
Milameline Drug Info Discontinued in Phase 3 Cognitive disorders [540021], [544882]
Terflavoxate Drug Info Discontinued in Phase 2 Urinary incontinence [545426]
A-72055 Drug Info Terminated Alzheimer disease [545007]
U-80816 Drug Info Terminated Amnesia [544857]
Modulator A-72055 Drug Info [550836]
DS-AH-14 Drug Info [550914]
Isopropamide iodide Drug Info [533466], [551871]
Milameline Drug Info [525615]
Oxybutynin hydrochloride Drug Info [525503], [551871]
PUR0200 Drug Info [550068]
RBx-343E48F0 Drug Info [543461]
Seebri Drug Info [533695]
Terflavoxate Drug Info [534003]
U-80816 Drug Info [550027]
Antagonist Alexa-488-telenzepine Drug Info [530688]
AZD-8683 Drug Info [543461]
AZD-9164 Drug Info [531685]
BODIPY-pirenzepine Drug Info [530147]
Cy3B-telenzepine Drug Info [530688]
EP-101 Drug Info [532169]
guanylpirenzepine Drug Info [525490]
hexahydrodifenidol Drug Info [533335]
hexahydrosiladifenidol Drug Info [533335]
Incruse Ellipta Drug Info [550959], [551871]
levetimide Drug Info [534549]
lithocholylcholine Drug Info [526426]
ML381 Drug Info [532729]
p-F-HHSiD Drug Info [534185]
QAX-028 Drug Info [550878]
silahexocyclium Drug Info [533335]
SMP-986 Drug Info [551635]
TD-4208 Drug Info [532360]
THRX160209 Drug Info [528817]
tripitramine Drug Info [533747]
UH-AH 37 Drug Info [534670]
VU0255035 Drug Info [530098]
[18F](R,R)-quinuclidinyl-4-fluoromethyl-benzilate Drug Info [534477]
[3H](+)telenzepine Drug Info [533336]
[3H]4NMPB Drug Info [533366]
[3H]AF DX-384 Drug Info [530102]
[3H]clidinium Drug Info [534549]
[3H]darifenacin Drug Info [534324]
[3H]N-methyl scopolamine Drug Info [526426]
[3H]pirenzepine Drug Info [533560]
[3H]QNB Drug Info [526153]
[3H]tiotropium Drug Info [532246]
Agonist APD-515 Drug Info [550192]
arecaidine propargyl ester Drug Info [534426]
AZD-2115 Drug Info [532016]
furtrethonium Drug Info [534426]
iperoxo Drug Info [532078]
LY593093 Drug Info [531470]
McN-A-343 Drug Info [533018]
methylfurmethide Drug Info [534426]
NNC 11-1314 Drug Info [526123]
NNC 11-1585 Drug Info [526123]
NNC 11-1607 Drug Info [526123]
oxotremorine-M Drug Info [534426]
pentylthio-TZTP Drug Info [534426]
THVD-201 Drug Info [544373]
[11C]butylthio-TZTP Drug Info [534227]
[11C]xanomeline Drug Info [534227]
[18F]FP-TZTP Drug Info [526587]
[3H]acetylcholine Drug Info [526926]
[3H]oxotremorine-M Drug Info [533556]
Modulator (allosteric modulator) benzoquinazolinone 12 Drug Info [532999]
brucine Drug Info [534573]
C7/3-phth Drug Info [534816]
dimethyl-W84 Drug Info [526650]
Duo3 Drug Info [527734]
Go7874 Drug Info [525801]
KT 5823 Drug Info [525801]
LY2033298 Drug Info [529629]
LY2119620 Drug Info [532770]
ML169 Drug Info [532128]
ML375 Drug Info [532524]
ML380 Drug Info [532927]
N-benzyl brucine Drug Info [534573]
N-chloromethyl-brucine Drug Info [534573]
thiochrome Drug Info [526926]
vinburnine Drug Info [534426]
VU0010010 Drug Info [529956]
VU0029767 Drug Info [529833]
VU0090157 Drug Info [529833]
VU0152099 Drug Info [529671]
VU0152100 Drug Info [529671]
W-84 Drug Info [526650]
WDuo3 Drug Info [526650]
WIN 51,708 Drug Info [526460]
WIN 62,577 Drug Info [526460]
[3H]dimethyl-W84 Drug Info [526650]
Inhibitor SUN-101 Drug Info [549743]
Pathways
KEGG Pathway Calcium signaling pathway
cAMP signaling pathway
Neuroactive ligand-receptor interaction
PI3K-Akt signaling pathway
Cholinergic synapse
Regulation of actin cytoskeleton
PathWhiz Pathway Muscle/Heart Contraction
Reactome Muscarinic acetylcholine receptors
Acetylcholine regulates insulin secretion
G alpha (q) signalling events
WikiPathways Monoamine GPCRs
Calcium Regulation in the Cardiac Cell
Regulation of Actin Cytoskeleton
GPCRs, Class A Rhodopsin-like
Gastrin-CREB signalling pathway via PKC and MAPK
Secretion of Hydrochloric Acid in Parietal Cells
GPCR ligand binding
GPCR downstream signaling
References
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Ref 522951ClinicalTrials.gov (NCT01068613) Safety and Efficacy of Multiple Doses of QAX028 in Chronic Obstructive Pulmonary Disease (COPD) Patients. U.S. National Institutes of Health.
Ref 523605ClinicalTrials.gov (NCT01426009) Study to Investigate the Dose Response, Safety and Efficacy of Nebulized EP-101 in Patients With Chronic Obstructive Pulmonary Disease (COPD): GOLDEN-1 Study. U.S. National Institutes of Health.
Ref 524096ClinicalTrials.gov (NCT01708057) A Single-dose Study to Investigate the Effects of 4 Different Doses of Inhaled AZD8683 in Chronic Obstructive Pulmonary Disease (COPD) Patients. U.S. National Institutes of Health.
Ref 524396ClinicalTrials.gov (NCT01921712) A Safety, Pharmacokinetic and Pharmacodynamic Study of PUR0200 in COPD Patients. U.S. National Institutes of Health.
Ref 524708ClinicalTrials.gov (NCT02109406) Efficacy and Safety Study of Two Dose Levels of AZD2115 in Subjects With Moderate to Severe COPD. U.S. National Institutes of Health.
Ref 524819ClinicalTrials.gov (NCT02181023) Acute Effect of Aclidinium on Hyperinflation and Ventilation Inhomogeneity in Severe COPD Patients. U.S. National Institutes of Health.
Ref 524970ClinicalTrials.gov (NCT02276222) A Long-Term Safety Trial of Treatment With Nebulized SUN-101 in Patients With COPD. U.S. National Institutes of Health.
Ref 525249ClinicalTrials.gov (NCT02485067) Clinical Study to Assess the Efficacy and Safety of THVD-201 in Patients With OAB.
Ref 525280ClinicalTrials.gov (NCT02512510) Efficacy Study of Nebulized TD-4208 for Chronic Obstructive Pulmonary Disease (COPD).
Ref 540021(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 301).
Ref 544857Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001336)
Ref 544882Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001410)
Ref 545007Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001856)
Ref 545426Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003221)
Ref 548182Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022820)
Ref 549205Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033659)
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 551969Clinical pipeline report, company report or official report of Novartis.
Ref 525490Subtypes of muscarinic receptors in rat duodenum: a comparison with rabbit vas deferens, rat atria, guinea-pig ileum and gallbladder by using imperialine. Gen Pharmacol. 1999 Apr;32(4):505-11.
Ref 525503Effects of propiverine hydrochloride (propiverine) on the muscarinic receptor binding affinity in guinea pig tissues and on salivation in conscious dogs. Nihon Yakurigaku Zasshi. 1999 Mar;113(3):157-66.
Ref 525615Milameline (CI-979/RU35926): a muscarinic receptor agonist with cognition-activating properties: biochemical and in vivo characterization. J Pharmacol Exp Ther. 1999 Nov;291(2):812-22.
Ref 525801Allosteric interactions of staurosporine and other indolocarbazoles with N-[methyl-(3)H]scopolamine and acetylcholine at muscarinic receptor subtypes: identification of a second allosteric site. Mol Pharmacol. 2000 Jul;58(1):194-207.
Ref 526123Synthesis and pharmacological evaluation of dimeric muscarinic acetylcholine receptor agonists. J Pharmacol Exp Ther. 2001 Sep;298(3):1260-8.
Ref 526153Interaction of anandamide with the M(1) and M(4) muscarinic acetylcholine receptors. Brain Res. 2001 Oct 5;915(1):70-8.
Ref 526426Lithocholylcholine, a bile acid/acetylcholine hybrid, is a muscarinic receptor antagonist. J Pharmacol Exp Ther. 2002 Oct;303(1):29-35.
Ref 526460Analogs of WIN 62,577 define a second allosteric site on muscarinic receptors. Mol Pharmacol. 2002 Dec;62(6):1492-505.
Ref 526587Regional brain uptake of the muscarinic ligand, [18F]FP-TZTP, is greatly decreased in M2 receptor knockout mice but not in M1, M3 and M4 receptor knockout mice. Neuropharmacology. 2003 Apr;44(5):653-61.
Ref 526650Interactions of orthosteric and allosteric ligands with [3H]dimethyl-W84 at the common allosteric site of muscarinic M2 receptors. Mol Pharmacol. 2003 Jul;64(1):180-90.
Ref 526926Thiochrome enhances acetylcholine affinity at muscarinic M4 receptors: receptor subtype selectivity via cooperativity rather than affinity. Mol Pharmacol. 2004 Jan;65(1):257-66.
Ref 527734Atypical muscarinic allosteric modulation: cooperativity between modulators and their atypical binding topology in muscarinic M2 and M2/M5 chimeric receptors. Mol Pharmacol. 2005 Dec;68(6):1597-610. Epub 2005 Sep 12.
Ref 528817A novel multivalent ligand that bridges the allosteric and orthosteric binding sites of the M2 muscarinic receptor. Mol Pharmacol. 2007 Aug;72(2):291-302. Epub 2007 May 3.
Ref 529629Allosteric modulation of the muscarinic M4 receptor as an approach to treating schizophrenia. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10978-83.
Ref 529671Centrally active allosteric potentiators of the M4 muscarinic acetylcholine receptor reverse amphetamine-induced hyperlocomotor activity in rats. J Pharmacol Exp Ther. 2008 Dec;327(3):941-53.
Ref 529833Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity. Mol Pharmacol. 2009 Mar;75(3):577-88.
Ref 529956Subtype-selective allosteric modulators of muscarinic receptors for the treatment of CNS disorders. Trends Pharmacol Sci. 2009 Mar;30(3):148-55.
Ref 530098A novel selective muscarinic acetylcholine receptor subtype 1 antagonist reduces seizures without impairing hippocampus-dependent learning. Mol Pharmacol. 2009 Aug;76(2):356-68.
Ref 530102Binding of [3H]AF-DX 384 to cloned and native muscarinic receptors. J Pharmacol Exp Ther. 1991 Nov;259(2):601-7.
Ref 530147Pirenzepine promotes the dimerization of muscarinic M1 receptors through a three-step binding process. J Biol Chem. 2009 Jul 17;284(29):19533-43.
Ref 530688Formation and dissociation of M1 muscarinic receptor dimers seen by total internal reflection fluorescence imaging of single molecules. Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2693-8.
Ref 531470Pharmacological characterization of LY593093, an M1 muscarinic acetylcholine receptor-selective partial orthosteric agonist. J Pharmacol Exp Ther. 2011 Aug;338(2):622-32.
Ref 531685The discovery of AZD9164, a novel muscarinic M3 antagonist. Bioorg Med Chem Lett. 2011 Dec 15;21(24):7440-6.
Ref 532016Evaluation of WO-2012085582 and WO-2012085583 two identified MABAs: backups to AZD-2115. Expert Opin Ther Pat. 2012 Nov;22(11):1377-83.
Ref 532078Agonists with supraphysiological efficacy at the muscarinic M2 ACh receptor. Br J Pharmacol. 2013 May;169(2):357-70.
Ref 532128Targeting selective activation of M(1) for the treatment of Alzheimer's disease: further chemical optimization and pharmacological characterization of the M(1) positive allosteric modulator ML169. ACS Chem Neurosci. 2012 Nov 21;3(11):884-95.
Ref 532169Long-acting muscarinic receptor antagonists for the treatment of respiratory disease. Pulm Pharmacol Ther. 2013 Jun;26(3):307-17.
Ref 532246Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases. J Pharmacol Exp Ther. 2013 May;345(2):260-70.
Ref 532360In vivo pharmacological characterization of TD-4208, a novel lung-selective inhaled muscarinic antagonist with sustained bronchoprotective effect in experimental animal models. J Pharmacol Exp Ther. 2013 Aug;346(2):241-50.
Ref 532524Discovery of the first M5-selective and CNS penetrant negative allosteric modulator (NAM) of a muscarinic acetylcholine receptor: (S)-9b-(4-chlorophenyl)-1-(3,4-difluorobenzoyl)-2,3-dihydro-1H-imidazo[2,1-a]isoindol-5(9bH)-one (ML375). J Med Chem. 2013 Nov 27;56(22):9351-5.
Ref 532729Discovery, synthesis and characterization of a highly muscarinic acetylcholine receptor (mAChR)-selective M5-orthosteric antagonist, VU0488130 (ML381): a novel molecular probe. ChemMedChem. 2014 Aug;9(8):1677-82.
Ref 532770Characterization of the novel positive allosteric modulator, LY2119620, at the muscarinic M(2) and M(4) receptors. Mol Pharmacol. 2014 Jul;86(1):106-15.
Ref 532927Development of a highly potent, novel M5 positive allosteric modulator (PAM) demonstrating CNS exposure: 1-((1H-indazol-5-yl)sulfoneyl)-N-ethyl-N-(2-(trifluoromethyl)benzyl)piperidine-4-carboxamide (ML380). J Med Chem. 2014 Sep 25;57(18):7804-10.
Ref 532999Mechanistic insights into allosteric structure-function relationships at the M1 muscarinic acetylcholine receptor. J Biol Chem. 2014 Nov 28;289(48):33701-11.
Ref 533018Pharmacological characterization of the M1 muscarinic receptors expressed in murine fibroblast B82 cells. J Pharmacol Exp Ther. 1989 Feb;248(2):661-70.
Ref 533335Antagonist binding properties of five cloned muscarinic receptors expressed in CHO-K1 cells. Mol Pharmacol. 1989 Apr;35(4):469-76.
Ref 533336The existence of stable enantiomers of telenzepine and their stereoselective interaction with muscarinic receptor subtypes. Mol Pharmacol. 1989 Apr;35(4):477-83.
Ref 533366Cloned M1 muscarinic receptors mediate both adenylate cyclase inhibition and phosphoinositide turnover. EMBO J. 1988 Oct;7(10):3031-5.
Ref 533466Competitive and non-competitive antagonism exhibited by 'selective' antagonists at atrial and ileal muscarinic receptor subtypes. Br J Pharmacol. 1987 Apr;90(4):701-7.
Ref 533556Solubilization and characterization of guanine nucleotide-sensitive muscarinic agonist binding sites from rat myocardium. Br J Pharmacol. 1984 Aug;82(4):853-61.
Ref 533560[3H]Pirenzepine identifies putative M1 muscarinic receptors in human stellate ganglia. Brain Res. 1984 Jan 2;290(1):179-82.
Ref 533695Glycopyrronium bromide blocks differentially responses mediated by muscarinic receptor subtypes. Naunyn Schmiedebergs Arch Pharmacol. 1993 Jun;347(6):591-5.
Ref 533747Binding profile of the selective muscarinic receptor antagonist tripitramine. Eur J Pharmacol. 1994 Aug 16;268(3):459-62.
Ref 534003Effects of terflavoxate on stimulated contractions of urinary bladder in vitro. Arzneimittelforschung. 1993 Feb;43(2):122-8.
Ref 534185Stimulation of cyclic AMP accumulation and phosphoinositide hydrolysis by M3 muscarinic receptors in the rat peripheral lung. Biochem Pharmacol. 1996 Aug 23;52(4):643-58.
Ref 534227PET study of the M1-agonists [11C]xanomeline and [11C]butylthio-TZTP in monkey and man. Dementia. 1996 Jul-Aug;7(4):187-95.
Ref 534324Characterisation of [3H]-darifenacin as a novel radioligand for the study of muscarinic M3 receptors. J Recept Signal Transduct Res. 1997 Jan-May;17(1-3):177-84.
Ref 534426Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors. Mol Pharmacol. 1997 Jul;52(1):172-9.
Ref 534477In vivo muscarinic binding selectivity of (R,S)- and (R,R)-[18F]-fluoromethyl QNB. Bioorg Med Chem. 1997 Aug;5(8):1555-67.
Ref 534549Pharmacological comparison of the cloned human and rat M2 muscarinic receptor genes expressed in the murine fibroblast (B82) cell line. J Pharmacol Exp Ther. 1998 Feb;284(2):500-7.
Ref 534573Subtype-selective positive cooperative interactions between brucine analogues and acetylcholine at muscarinic receptors: radioligand binding studies. Mol Pharmacol. 1998 Mar;53(3):573-89.
Ref 534670Comparison of the in vitro and in vivo profiles of tolterodine with those of subtype-selective muscarinic receptor antagonists. Eur J Pharmacol. 1998 May 22;349(2-3):285-92.
Ref 534816Characterization of the subtype selectivity of the allosteric modulator heptane-1,7-bis-(dimethyl-3'-phthalimidopropyl) ammonium bromide (C7/3-phth) at cloned muscarinic acetylcholine receptors. Biochem Pharmacol. 1999 Jan 15;57(2):171-9.
Ref 543461(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 17).
Ref 544373Future therapies: Early trials and basic science. Can Urol Assoc J. 2013 Sep-Oct; 7(9-10 Suppl 4): S179-S180.
Ref 549743Long-acting bronchodilators in COPD: Where are we now and where are we going? Breathe 06/2014; 10(2):110-120.
Ref 550027U-80816: A novel partial muscarinic agonist. Drug Development Research Volume 24, Issue 1, pages 53-66, 1991.
Ref 550068Clinical pipeline report, company report or official report of pulmatrix pipeline.
Ref 550192Clinical pipeline report, company report or official report of Acacia Pharma.
Ref 550836US patent application no. 2011,0020,423, Methods and compositions for treatment of disorders ameliorated by muscarinic receptor activation.
Ref 550878EP patent application no. 2398798, Triazolopyridine derivatives as p38 map kinase inhibitors.
Ref 550914US patent application no. 5,446,057, Substituted tetrahydropyridine and piperidine carboxylic acids as muscarinic antagonists.
Ref 550959Clinical pipeline report, company report or official report of GlaxoSmithKline.
Ref 551635DUAL INHIBITION OF Na+-CHANNEL AND MUSCARINIC RECEPTORS BY SMP-986 EFFICIENTLY IMPROVED VOIDING FUNCTION COMPARED TO ANTI-MUSCARINIC AGENTS IN TWO CONSCIOUS RAT MODELS OF DETRUSOR OVERACTIVITY. The Journal of Urology Volume 179, Issue 4, Supplement, April 2008, Pages 129.
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

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