mAChR Inhibitor

Ebelin lactone is an acetylcholinesterase (AChE) inhibitor, with a K_i of 0.45 μM against human M1 muscarinic acetylcholine receptor (mAChR) and a K_i of 4.21 μM against human 5-HT2A serotonin receptor. Ebelin lactone binds to the allosteric cavity above the orthosteric site of M1 via nonpolar interactions with subtype-selective residues. Ebelin lactone binds to the cavity between transmembrane helices 4 and 5 of 5-HT2A through nonpolar interactions with orthosteric site residues. Ebelin lactone exhibits free radical scavenging activity, inhibits cancer cell proliferation, and regulates memory and cognitive processes by interacting with M1 and 5-HT2A receptors. Ebelin lactone can be used in studies related to Alzheimer's disease, breast cancer and colorectal cancer.

Benztropine mesylate (Benzatropine mesylate) is an orally active and BBB-permeable centrally acting anticholinergic agent that can be used for Parkinson's disease research. Benztropine mesylate is an anti-histamine agent and a dopamine re-uptake inhibitor. Benztropine mesylate is also a human D₂ dopamine receptor allosteric antagonist. Benztropine mesylate also has anti-CSCs (cancer stem cells) effects.

Methscopolamine bromide ((-)-Scopolamine methyl bromide; Hyoscine methyl bromide) is a peripherally acting muscarinic receptor (mAChR) antagonist that cannot cross the blood-brain barrier. Methscopolamine bromide blocks the muscarinic negative feedback regulation of acetylcholine release from striatal cholinergic terminals, thereby increasing acetylcholine release in the striatum of freely moving rats. Methscopolamine bromide does not induce motor excitation in freely moving rats, nor does it alter the duration of ethanol-induced loss of righting reflex in mice. Methscopolamine bromide fails to antagonize the arecoline-mediated reduction in the duration of ethanol-induced loss of righting reflex in mice.

Dronedarone (SR 33589), a derivative of amiodarone (HY-14187), is a class III antiarrhythmic agent for the study of atrial fibrillation (AF) and atrial flutter. Dronedarone is a potent blocker of multiple ion currents, including potassium current, sodium current, and L-type calcium current, and exhibits antiadrenergic effects by noncompetitive binding to β-adrenergic receptors. Dronedarone is a substrate for and a moderate inhibitor of CYP3A4.

Otilonium bromide (OB) is an orally active mAChR inhibitor and smooth muscle relaxant which can interfere with the mobilization of calcium in intestinal smooth muscle, OB can be used for research of irritable bowel syndrome.

(-)-Vesamicol (AH5183) is a vesicular acetylcholine transporter inhibitor. (-)-Vesamicol reversibly and non-competitively inhibits the transport of acetylcholine into circulating synaptic vesicles and blocks the activity of vesicular acetylcholine transporters in medial amygdala neurons. (-)-Vesamicol is applicable to research related to central precocious puberty.

Biperiden (KL 373) is a non-selective muscarinic receptor antagonist that competitively binds to M1 muscarinic receptors, thereby inhibiting acetylcholine and enhancing dopamine signaling in the central nervous system. Biperiden has the potential for the research of Parkinson's disease and other related psychiatric disorders.

BQCA a highly selective allosteric modulator of the M1 mAChR.

ML375 (VU0483253) is a potent, highly selective, brain-penetrant and orally active M5 mAChR negative allosteric modulator (NAM) with IC₅₀s of 300 nM and 790 nM for human and rat M5, respectively. ML375 is inactive at human and rat M1-M4.

Biperiden (KL 373) hydrochloride is a non-selective muscarinic receptor antagonist that competitively binds to M1 muscarinic receptors, thereby inhibiting acetylcholine and enhancing dopamine signaling in the central nervous system. Biperiden hydrochloride has the potential for the research of Parkinson's disease and other related psychiatric disorders.

Imidafenacin (KRP-197; ONO-8025) is an orally active inhibitor of muscarinic (mAChR) M₁ and M₃ receptors. Imidafenacin potently inhibits bladder contraction in vivo and exerts an antidiuretic effect by enhancing the signaling pathway of vasopressin (antidiuretic hormone). Imidafenacin can be used in research related to overactive bladder.

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).

Dicyclomine hydrochloride is a potent and orally active muscarinic cholinergic receptors antagonist. Dicyclomine hydrochloride shows high affinity for muscarinic M1 receptor subtype (K_i=5.1 nM) and M2 receptor subtype (K_i=54.6 nM) in brush-border membrane and basal plasma membranes, respectively. Dicyclomine is an antispasmodic agent and relieves smooth muscle spasm of the gastrointestinal tract in vivo.

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.

Gallamine Triethiodide is a blood-brain barrier-permeable skeletal muscle relaxant. Gallamine Triethiodide induces skeletal muscle paralysis by blocking acetylcholine. Gallamine Triethiodide directly stimulates intracardiac β receptors. Gallamine Triethiodide prolongs the duration of afterdischarge in the cat cerebral cortex. Gallamine Triethiodide can be used in studies related to convulsive disorders.

Arborine inhibits the peripheral action of acetylcholine and induces a fall in blood pressure.

Propiverine hydrochloride is a bladder spasmolytic with calcium antagonistic and anticholinergic properties. Propiverine hydrochloride can be used for the research of overactive blaqdder and urinary incontinence.

Brompheniramine ((±)-Brompheniramine) maleate is a potent and orally active antihistamine of the alkylamine class. Brompheniramine maleate is a selective histamine H1 receptor antagonist with a K_d of 6.06 nM. Brompheniramine maleate can block the hERG channels, calcium channels, and sodium channels with IC₅₀s of 0.90 μM, 16.12 μM and 21.26 μM, respectively. Brompheniramine maleate has anticholinergic, antidepressant and anesthetic properties and can be used for allergic rhinitis research.

Methylbenactyzium Bromide is a muscarinic acetylcholine receptor (mAChR) inhibitor.

Benztropine (Benzatropine; Benzotropine) is an orally active and BBB-permeable centrally acting anticholinergic agent that can be used for Parkinson's disease research. Benztropine is an anti-histamine agent and a dopamine re-uptake inhibitor. Benztropine is also a human D₂ dopamine receptor allosteric antagonist. Benztropine mesylate also has anti-CSCs (cancer stem cells) effects.