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].
[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].
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.
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
Scopolamine butylbromide is a competitive antagonist of muscarinic acetylcholine receptor (mAChR) with an IC50 of 55.3 ± 4.3 nM.Target: mAChRScopolamine (USAN), also known as levo-duboisine and hyoscine, sold as Scopoderm, is a tropane alkaloid drug with muscarinic antagonist effects. It is among the secondary metabolites of plants from Solanaceae (nightshade) family of plants, such as henbane, jimson weed (Datura), angel's trumpets (Brugmansia), and corkwood (Duboisia). Scopolamine exerts its effects by acting as a competitive antagonist at muscarinic acetylcholine receptors, specifically M1 receptors; it is thus classified as an anticholinergic, antimuscarinic drug. Its use in medicine is relatively limited, with its chief uses being in the treatment of motion sickness and postoperative nausea and vomiting. Scopolamine is named after the plant genus Scopolia. The name "hyoscine" is from the scientific name for henbane, Hyoscyamus niger.
Penehyclidine (Penequinine) hydrochloride, a anticholinergic drug, is a selective antagonist of M1 and M3 receptors. Penehyclidine hydrochloride activates NF-kβ in lung tissue and inhibits the release of inflammatory factors. Penehyclidine hydrochloride can alleviate the pulmonary inflammatory response in rats with chronic obstructive pulmonary disease (COPD) undergoing mechanical ventilation[1].
Rispenzepine is a novel antimuscarinic compound with a preferential action at M1, and M3 receptor subtypes.
(R)-Oxybutynin hydrochloride, a (R)-isomer of Oxybutynin hydrochloride, is an orally active muscarinic receptor antagonist. (R)-Oxybutynin hydrochloride has antimuscarinic, antispasmodic and anticholinergic activity, competitively antagonizes Carbachol-induced contractions. (R)-Oxybutynin hydrochloride can be used for researching incontinence due to neurogenic bladder dysfunction[1][2][3].
PCS1055 dihydrochloride is a potent, selective and competitive muscarinic M4 receptor antagonist with an IC50 of 18.1 nM and a Kd of 5.72 nM. PCS1055 dihydrochloride inhibits radioligand [3H]-NMS binding to the M4 receptor with a Ki of 6.5 nM. PCS1055 dihydrochloride exhibits >100-fold selectivity over M1-, M3-, and M5-receptors and 30-fold selectivity at the M2 receptor. PCS1055 dihydrochloride is also a potent AChE inhibitor with IC50 s of 22 nM and 120 nM for electric eel and human AChE, respectively[1][2].
Dicyclomine hydrochloride is a potent and orally active muscarinic cholinergic receptors antagonist. Dicyclomine hydrochloride shows high affinity for muscarinic M1 receptor subtype (Ki=5.1 nM) and M2 receptor subtype (Ki=54.6 nM) in brush-border membrane and basal plasma membranes, respectively[1]. Dicyclomine is an antispasmodic agent and relieves smooth muscle spasm of the gastrointestinal tract in vivo[2].
Oxotremorine sesquifumarate is a mAChR agonist that mainly activates M2 receptors. Oxotremorine sesquifumarate can be used for neurological research[1][2].
Arecaidine but-2-ynyl ester tosylate is a potent muscarinic agonist that shows 4.6-fold that is selectivity for mAChR M2 in the atrium versus those in the ileum.
Telenzepine is an antimuscarinic agent with Kis of 0.94 nM (M1 mAChR) and 17.8 nM (M2 mAChR) binding to muscarinic receptors. Telenzepine effectively blocks synaptic transmission promoted by muscarinic or M1 receptor agonists. Thus, Telenzepine can reduce the amplitude of extracellular slow excitatory postsynaptic potentials (EC50=38 nM) and slow inhibitory postsynaptic potentials (EC50=253 nM)[1].
RHC 80267 (U-57908) is a potent and selective inhibitor of diacylglycerol lipase (DAGL) (with IC50 of 4 μM in canine platelets). RHC-80267 inhibits cholinesterase activity with an IC50 of 4 μM, thereby enhancing the relaxation evoked by acetylcholine. RHC 80267 also inhibits COX and the hydrolysis of phosphatidylcholine (PC)[1][2][3][4].
PF-06827443 (PF06827443) is a potent, orally bioavailable, and CNS-penetrant M1-selective positive allosteric modulator (PAM) with EC50 of 47 nM, shows no activity against M2-M5 at 10 uM; induces cholinergic adverse events and convulsion at therapeutic indices similar to previous compounds with more agonist activity.
Cimetropium Bromide is a mAChR antagonist for long-term treatment of irritable bowel syndrome.
AF-DX 384 is a selective antagonist of M2 and M4 muscarinic acetylcholine receptors (Kis=6.03 and 10 nM, respectively)[1]. AF-DX 384 reverses deficits in novel object recognition and passive avoidance in aged rats, as well as in young rats with impairments induced by scopolamine[2].
(R)-VU 6008667, an active enantiomer of VU6008667, is a orally active acetylcholine receptor subtype 5 (M5 NAM) inhibitor with IC50 values of 1.2 μM (human) and 1.6 μM (rat), respectively. (R)-VU6008667 is selective for M5 over M1-4, high CNS penetration[1].
Tolterodine Tartrate(PNU-200583E; Kabi-2234) is a potent muscarinic receptor antagonists that show selectivity for the urinary bladder over salivary glands in vivo. IC50 Value:Target: mAChRin vitro: Carbachol-induced contractions of isolated guinea pig bladder were effectively inhibited by tolterodine (IC50 14 nM) and 5-HM (IC50 5.7 nM). The IC50 values were in the microM range and the antimuscarinic potency of tolterodine was 27, 200 and 370-485 times higher, respectively, than its potency in blocking histamine receptors, alpha-adrenoceptors and calcium channels. The active metabolite, 5-HM, was >900 times less potent at these sites than at bladder muscarinic receptors [1].in vivo: Tolterodine was extensively metabolized in vivo [2]. In the passive-avoidance test, tolterodine at 1 or 3 mg/kg had no effect on memory; the latency to cross and percentage of animals crossing were comparable to controls. In contrast, scopolamine induced a memory deficit; the latency to cross was decreased, and the number of animals crossing was increased [3].
Zamifenacin fumarate (UK-76654 fumarate) is a potent gut-selective muscarinic M3 receptor antagonist. Zamifenacin significantly reduces colonic motility in irritable bowel syndrome[1].
Anagyrine ((-)-Anagyrine) hydrochloride is a quinolizidine alkaloid that has been found in Lupinus albus. Anagyrine hydrochloride binds to muscarinic and nicotinic acetylcholine receptors with IC50 values of 132 and 2096 µM respectively. Anagyrine hydrochloride is a potent and effective desensitizer of nAChR, and Anagyrine hydrochloride can directly, without metabolism, desensitize nAChR[1][2][3].
AC-42 is a poent M1 muscarinic selective allosteric agonist with EC50s of 805 nM and 220 nM for human wild-type and Y381A mutated M1 receptors, respectively[1].
Clozapine-d4 (HF 1854-d4) is the deuterium labeled Clozapine. Clozapine is an antipsychotic used for the research of schizophrenia. Clozapine has high affinity for a number of neuroreceptors[1][2][3][4][5].
Tolterodine(PNU-200583) is a potent muscarinic receptor antagonists that show selectivity for the urinary bladder over salivary glands in vivo. IC50 Value:Target: mAChRin vitro: Carbachol-induced contractions of isolated guinea pig bladder were effectively inhibited by tolterodine (IC50 14 nM) and 5-HM (IC50 5.7 nM). The IC50 values were in the microM range and the antimuscarinic potency of tolterodine was 27, 200 and 370-485 times higher, respectively, than its potency in blocking histamine receptors, alpha-adrenoceptors and calcium channels. The active metabolite, 5-HM, was >900 times less potent at these sites than at bladder muscarinic receptors [1].in vivo: Tolterodine was extensively metabolized in vivo [2]. In the passive-avoidance test, tolterodine at 1 or 3 mg/kg had no effect on memory; the latency to cross and percentage of animals crossing were comparable to controls. In contrast, scopolamine induced a memory deficit; the latency to cross was decreased, and the number of animals crossing was increased [3].
β2AR/M-receptor agonist-2 (compound 15) is a muscarinic antagonist and β2 adrenoceptor agonist (MABA). β2AR/M-receptor agonist-2 shows potency to β2 adrenoceptor with an EC50 value of 3.7 nM. β2AR/M-receptor agonist-2 also has potency to human cloned M3 receptor with a Ki value of 0.73 nM. β2AR/M-receptor agonist-2 is a potent bronchodilator, it can be used for the research of chronic obstructive pulmonary disease (COPD)[1].
Atropine sulfate monohydrate is a competitive muscarinic acetylcholine receptor antagonist.Target: mAChRAtropine is a naturally occurring tropane alkaloid extracted from deadly nightshade (Atropa belladonna), Jimson weed (Datura stramonium), mandrake (Mandragora officinarum) and other plants of the family Solanaceae. Atropine is a competitive antagonist of the muscarinic acetylcholine receptors (acetylcholine being the main neurotransmitter used by the parasympathetic nervous system). Atropine dilates the pupils, increases heart rate, and reduces salivation and other secretions [1].
Trihexyphenidyl hydrochloride is an antiparkinsonian agent of the antimuscarinic class, binds to the M1 muscarinic receptor.
L-Hyoscyamine sulfate (Daturine sulfate) is a tropane alkaloid that is a secondary metabolite found in certain plants of the solanaceae family. In vitro it has been shown to be an antagonist of mAChR[1].