Solifenacin D5 hydrochloride is a deuterium labeled Solifenacin hydrochloride. Solifenacin hydrochloride is a muscarinic receptor antagonist with pKis of 7.6, 6.9 and 8.0 for M1, M2 and M3 receptors, respectively[1].
Methacholine chloride is a synthetic choline ester that acts as a non-selective muscarinic receptor agonist in the parasympathetic nervous system.
Irsogladine is a PDE4 inhibitor and muscarinic acetylcholine receptor binder.Target: PDE4; mACHRIrsogladine treatment (300 and 500 mg/kg/day) resulted in a dose-dependent reduction of angiogenesis in wild-type mice by 21 and 45.3% (P < 0.02, P < 0.001), in tPA-deficient mice by 42.6 and 46% (P < 0.001, P < 0.001), and in uPA-deficient mice by 27.2 and 46% (P < 0.05, p < 0.001), respectively. Irsogladine inhibits bFGF-induced angiogenesis in wild-type, tPA-knockout, and uPA-knockout mice [1]. Irsogladine up-regulates GJIC between PC cells via regulation of the PKA pathway. It also suggests a useful adjuvant of Irsogladine to pancreatic cancer therapy [2]. irsogladine produces the increase of intracellular cAMP content via non-selective inhibition of PDE isozymes, which may be a key mechanism involved in its gastroprotective actions [3].
Sofpironium bromide (BBI 4000) is an anticholinergic agent used in the study of primary axillary hyperhidrosis (PAH). Sofpironium bromide reduces sweating by inhibiting M3 muscarinic receptors in eccrine glands at the application site. Sofpironium bromide also has a high afnity for the M1, M2, M4 and M5 subtypes[1].
LAS190792 (AZD8999) is a potent muscarinic antagonist and β2-adrenoceptor agonist with pIC50 8.9, 8.8, 8.8, 9.2, 8.2, 7.5, 9.1, 5.6 for M1, M2, M3, M4, M5, β1, β2, β3, respectively. LAS190792 can be used as a bronchodilatorsup>[1].
Benzamide Derivative 1 is a benzamide derivative from patent EP0213775A1, compound 18. Benzamide Derivative 1 may be useful in treatment of gastrointestinal disorders.
Tropicamide is an anticholinergic and a muscarinic receptor subtype M4-preferring antagonist .Target: mAChRTropicamide is an antimuscarinic drug that produces short acting mydriasis (dilation of the pupil) and cycloplegia when applied as eye drops. It is used to allow better examination of the lens, vitreous humor, and retina. Due to its relatively short duration of effect (4-8 hours), it is typically used during eye examinations such as the dilated fundus examination, but it may also be used before or after eye surgery. Cycloplegic drops are often also used to treat anterior uveitis, decreasing risk of posterior synechiae and decreasing inflammation in the anterior chamber of the eye [1-3].
YM-46303 is an mAChR antagonist which exhibits the highest affinities for M1 and M3 receptors, and selectivity for M3 over M2 receptor.
Aclidinium Bromide(LAS 34273; LAS-W 330) is a long-acting, inhaled muscarinic antagonist as a maintenance treatment for chronic obstructive pulmonary disease (COPD). IC50 value:Target: M3 receptorPreclinically, aclidinium showed potent antagonism of human muscarinic receptors, with a long residence time at M3 receptors and a shorter residence time at M2 receptors, indicating the potential to provide sustained bronchodilation. Aclidinium is rapidly hydrolysed in human plasma, unlike other currently available antimuscarinics including tiotropium. Early clinical studies in healthy subjects have confirmed the low systemic bioavailability and favourable safety profile of single and multiple doses of aclidinium. In a subsequent Phase IIb study, which included 464 patients with moderate to severe COPD, aclidinium displayed long-lasting bronchodilatory activity and was well tolerated.
M1 ligand 1 (compound 3b-b) is a muscarinic acetylcholine receptor M1 ligand. M1 ligand 1 is a N-desmethyl congener of arecoline derivative. M1 ligand 1 can be used as PET (positron emission tomography) radiotracer[1].
ML169 (VU0405652) is a potent, selective and brain penetrant positive allosteric modulator (PAM) of M1 mAChR, with an EC50 of 1.38 µM. ML169 is a MLPCN probe and can be used for Alzheimer’s disease[1].
Tiotropium Bromide (BA679 BR) is a muscarinic acetylcholine receptor (mAChR) antagonist that blocks the binding of the acetylcholine ligand and subsequent opening of the ligand-gated ion channel.
Flavoxate is a potent and competitive phosphodiesterase (PDE) inhibitor. Flavoxate is an antispasmodic agent and muscarinic mAChR antagonist. Flavoxate shows moderate calcium antagonistic activity and local anesthetic effect. Flavoxate can be used for the research of overactive bladder (OAB) and lower urinary tract infections[1][2].
Racanisodamine is one of the racemic isomers of anisodamine, resembles anisodamine in pharmacological effect. Racanisodamine is a non-selective muscarinic antagonist, used as a component of eye drops for myopic control[1].
Flavoxate Hydrochloride(DW-61 Hydrochloride) is a muscarinic AChR antagonist used in various urinary syndromes and as an antispasmodic.Target: mAChRFlavoxate displaces [3H]nitrendipine on the Ca2+ channels binding sites with IC50 of 254 μM [1]. Flavoxate (>10 μM) suppresses carbachol-induced contractions in isolated rat detrusor strips with pD value of 4.55. Flavoxate (>10 μM) suppresses Ca2+-induced contractions in isolated rat detrusor strips with pIC50 value of 4.92 [2]. Flavoxate (0.01 μM ?10 μM) inhibits CAMP formation in a concentration-dependent manner in membranes from the rat striatum and cerebral cortex, an action which is completely abolished by pretreating the membranes with pertussis toxin (PTX) [3].Flavoxate (10mg/kg) suppresses both the an initial, rapidly rising phasic contraction (phase 1) and the tonic contraction (phase 2) contractions to the same extent in rats. Flavoxate (10mg/kg) abolishes the bladder contractions without causing any change in the amplitude of the contractions in rats. Flavoxate (3 mg/kg) abolishes the efferent neural activity and the associated bladder contractions for about 10 minutes without changing the baseline vesical pressure in rats. ICV-injected (50 to 200 μg/rat) or IT-injected (100 to 200 μg/rat) Flavoxate abolishes rhythmic bladder contractions during and after injection for five to 15 minutes in a dose-dependent manner in rats [2]. Flavoxate (3 mg/kg, i.v.) abolishes rhythmic bladder contractions and the maximal intervals of voiding contractions is 7.20 min [3].
Darenzepine is a muscarinic receptor inhibitor extracted from patent US 20170095465 A1.
Tridihexethyl (Pathilon) chloride is an orally active anticholinergic agent and mAChR antagonist, shows activities of antimuscarinic and anticholinergic. Tridihexethyl chloride shows pronounced antispasmodic and antisecretory effects on the gastrointestinal tract. Tridihexethyl chloride can be used in studies of peptic ulcer disease and acquired nystagmus [1][2].
Oxyphenonium bromide is an antiacetylcholine compound. Oxyphenonium bromide is an antagonist of mAChR. Oxyphenonium bromide protects against the bronchial obstructive effects[1][2][3].
WIN 64338 hydrochloride is a potent, selective, nonpeptide competitive antagonist of bradykinin B2 receptor. WIN 64338 hydrochloride inhibits [3H]-Bradykinin binding to the bradykinin B2 receptor on human IMR-90 cells with a Ki of 64 nM. WIN 64338 hydrochloride also can inhibits [3H]Quinuclidinyl benzilate binding to the rat brain muscarinic receptor (Ki=350 nM)[1][2].
Cycrimine is an orally active muscarinic cholinergic receptor (mAChR) M1 antagonist, reduces the acetylcholine levels in parkinson model. Cycrimine shows antispasmodic activity, can be used in studies of behavioral and mental disorder[1][2][3][4].
[D-Trp7,9,10]-Substance P is the substance P analog that inhibits activation of Gq/11 by M1 muscarinic ACh receptors. [D-Trp7,9,10]-Substance P does not inhibit Gi/o activation by M2 ACh receptors.
RLH-033 is a potent and selective ligand for the sigma 1 recognition site. RLH-033 has high affinity for sigma 1 sites labeled by [3H](+)-pentazocine with a Ki of 50 pM[1].
Piperidolate is an antimuscarinic, inhibits intestinal cramp induced by acetylcholine (rats and dogs).
VU0238441 is a pan muscarinic acetylcholine receptor (mAChR) positive allosteric modulator (PAM) with EC50s of 3.2 μM, 2.8 μM, 2.2 μM, 2.1 μM, >10 μM for M1, M2, M3, M5 and M4, respectively[1][2].
Trospium Chloride is a competitive muscarinic cholinergic receptor antagonist.Target: mAChRTrospium chloride is an antimuscarinic agent indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. Trospium has pharmacologic properties that are distinct from other antimuscarinic agents [1]. After oral administration, absorption of the hydrophilic trospium chloride is slow and incomplete. Peak plasma concentrations (Cmax) of approximately 4 ng/mL are reached 4-5 hours after administration of a 20 mg immediate-release preparation. The mean bioavailability is approximately 10% and decreases by concomitant food intake (to a mean of 26% of the fasting area under the plasma concentration-time curve [AUC]). Trospium chloride displays dose proportional increases in AUC and Cmax after a single dose within the clinically relevant dose range (20-60 mg). The mean volume of distribution is approximately 350-800 L [2].
β2AR/M-receptor agonist-1 (example 131) is a muscarinic antagonist and β2 adrenoceptor agonist (MABA). β2AR/M-receptor agonist-1 shows potency to β2 adrenoceptor with an EC50 value of 9.2 nM. β2AR/M-receptor agonist-1 also has potency to muscarinic receptor with a Ki value of 30.2 nM. β2AR/M-receptor agonist-1 shows MABA potency with an EC50 value of 4.0 nM[1].
Pilocarpine-d3 (hydrochloride) is deuterium labeled Pilocarpine (Hydrochloride). Pilocarpine Hydrochloride is a potent M3-type muscarinic acetylcholine receptor (M3 muscarinic receptor) agonist.
(S)-(+)-Dimethindene maleate, an enantiomer, is a potent M2-selective muscarinic receptor antagonist (pA2 = 7.86/7.74; pKi = 7.78). (S)-(+)-Dimethindene maleate shows lower affinities for the muscarinic M1 (pA2 = 6.83/6.36; pKi = 7.08), the M3 (pA2 = 6.92/6.96; pKi = 6.70) and the M4 receptors (pKi = 7.00), respectively. (S)-(+)-Dimethindene maleate also is a histamine H1 receptor antagonist (pA2 = 7.8)[1].
Dronedarone(Multaq) is a newer therapeutic agent with a structural resemblance to amiodarone and a better side effect profile; it is a multichannel blocker with antiadrenergic properties and has been evaluated in both rate and rhythm control strategies in the management of AF.IC50 value:Target: multichannel blocker