Cyclodrine hydrochloride is a cholinergic (muscarinic, nicotinic) (mAChR and nAChR) receptor antagonist.
VU6028418 (VU 6028418) is a potent, highly selective, orally bioavailable M4 mAChR antagonist for the treatment of dystonia and other movement disorders.
Octamylamine is an anticholinergic and antispasmodic agent[1].
BTM-1086 is a potent anti-ulcer and gastric secretory inhibiting agent.
Otilonium Bromide is an antimuscarinic used as a spasmolytic agent.Target: mAChROtilonium bromide inhibited the generation of ACh-induced calcium signals in a dose dependent manner (IC50=880 nM) [1]. Otilonium, a clinically useful spasmolytic, behaves as a potent blocker of neuronal nicotinic acetylcholine receptors (AChR). Whole-cell Ba2+ currents (IBa) through Ca2+ channels of voltage-clamped chromaffin cells were blocked by otilonium with an IC50 of 6.4 microM. Otilonium inhibited the secretory responses induced by 10 s pulses of 50 microM DMPP with an IC50 of 7.4 nM [2]. Otilonium bromide may represent an effective treatment for irritable bowel syndrome because it reduces its predominant symptom (abdominal pain/ discomfort) more than placebo does [3]. ilonium bromide (OB) is a spasmolytic agent that blocks L-Type Calcium channels in human colonic smooth muscle. otilonium bromide is safe, well tolerated and superior to placebo in reducing the frequency of abdominal pain, severity of abdominal bloating and protecting from symptom relapse in IBS. These results further confirm that patients with IBS can improve during and following treatment with otilonium bromide [4].
VU0152100 is a potent and selective allosteric potentiator of M4 mAChR with an EC50 of 380 ± 93 nM.IC50 Value: 380 ± 93 nM (EC50) [1]Target: M4 mAChRin vitro: VU0152100 was selective for M4 relative to M1, M2, M3, and M5. VU0152100 dose-dependently potentiated the response to an EC20 concentration of ACh with EC50 values of 1.9 ± 0.2 μM, and increased the maximal response to ACh to approximately 130%. VU0152100 (10 μM) also enhanced the potency of ACh to induce GIRK-mediated thallium flux, as manifest by a robust (≈30-fold) leftward shift in the ACh CRC from 77 ± 1.2 nM (veh) to 2.35 ± 0.5 nM (VU0152100) [1].in vivo: Systemic administration of VU0152099 and VU0152100 provides robust brain levels of these compounds, the effects of VU0152099 and VU0152100 were evaluated in reversing amphetamine-induced hyperlocomotion in rats using a dose of 56.6 mg/kg i.p. for each compound with a 30-min pretreatment interval [1].
Biperiden(KL 373) Hcl is an antiparkinsonian agent, which is the selective central M1 cholinoreceptors blocker.Target: M1 receptorsBiperiden is an antiparkinsonian agent of the anticholinergic type. It is used for the adjunctive treatment of all forms of Parkinson's disease (postencephalitic, idiopathic, and arteriosclerotic)[1]. Biperiden has an atropine-like blocking effect on all peripheral structures which are parasympathetic-innervate. It also has a prominent central blocking effect on M1 receptors [2].Biperiden (0.11 mg/kg), benactyzine (0.3 mg/kg),caramiphen (10 mg/kg), procyclidine (3 mg/kg), and trihexyphenidyl (0.12 mg/kg) separately and each in combination with physostigmine (0.1 mg/kg) is to make a comparative assessment of potential cognitive effects. The results showed that benactyzine, caramiphen, and trihexyphenidyl reduced rats' innate preference for novelty, whereas biperiden and procyclidine did not [3].Clinical indications: parkinsonismFDA Approved Date: Toxicity: Drowsiness; vertigo; headache; dizziness
Solifenacin Hcl(YM905 Hcl; Vesicare Hcl) is a muscarinic receptor antagonist.IC50 value:Target: muscarinic receptorSolifenacin Hcl (YM905; Vesicare) is a prescription medication used to treat certain bladder problems.
Bethanechol Chloride is a selective muscarinic receptor agonist without any effect on nicotinic receptors.Target: mAChRBethanechol is a parasympathomimetic choline carbamate that selectively stimulates muscarinic receptors without any effect on nicotinic receptors. Unlike acetylcholine, bethanechol is not hydrolyzed by cholinesterase and will therefore have a long duration of action. Oral bethanechol significantly improves contraction pressures and bolus transit in the smooth muscle portion of the esophagus in patients with severe IEM [1]. Bethanechol has potential benefit in the treatment of cerebral palsy [2].
Alvameline (Lu25-109) is a partial M1 agonist and M2/M3 antagonist.
Pirmenol hydrochloride inhibits IK.ACh by blocking muscarinic receptors. The IC50 of Pirmenol for inhibition of Carbachol-induced IK.ACh is 0.1 μM.
Ipratropium bromide (Sch 1000) hydrate is a muscarinic receptor antagonist, with IC50s of 2.9 nM, 2 nM, and 1.7 nM for M1, M2, and M3 receptors, respectively. Ipratropium bromide hydrate relaxes smooth muscle, can be used in the research for COPD (chronic obstructive pulmonary disease) and asthma[1][2][3][4][5].
Metixene hydrochloride hydrate is an anticholinergic antiparkinsonian agent, potently inhibits binding of quinuclidinyl benzilate (QNB) to the muscarinic receptor in rat brain cortical tissue, with an IC50 of 55 nM and a Kd of 15 nM[1].
VU0119498 is a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM), with EC50s of 6.04, 6.38, and 4.08 µM, respectively. VU0119498 has antidiabetic activity[1][2][3].
Quifenadine (Compound 3a), the hydroxyl-(diphenyl)methyl quinuclidine derivative, is a M3 receptor antagonist with an IC50 value > 1000 nM. Quifenadine can be used for the research of neurological disease[1].
BQCA a highly selective allosteric modulator of the M1 mAChR.
Clozapine (HF 1854) is an antipsychotic used to treat schizophrenia. Clozapine is a potent antagonist of dopamine and a number of other receptors, with a Ki of 9.5 nM for M1 receptor.
Muscarine ((+)-Muscarine) chloride is a toxin that can stimulate the parasympathetic nervous system. Muscarine is a prototype muscarinic acetylcholine receptor agonist[1][2].
VU 6008667 is a selective negative allosteric modulator of muscarinic acetylcholine receptor subtype 5 (M5 NAM) with IC50s of 1.2 μM and 1.6 μM for human M5 and rat M5, respectively. VU 6008667 has high CNS penetration[1].
Beperidium iodide shows a competitive antagonistic effect against acetylcholine receptor with a pA2 of 7.93.
Oxyphencyclimine is an orally active muscarinic receptor (mAChR) antagonist. Oxyphencyclimine is effective in reducing ulceration index and increasing pepsin activity in rat gastric ulcer model. Oxyphencyclimine can be used in studies of peptic ulcer disease and gastrointestinal spasm[1][2].
L-Hyoscyamine is a chemical compound, a tropane alkaloid it is the levo-isomer to atropine.Target: mAChRHyoscyamine is a chemical compound, a tropane alkaloid it is the levo-isomer to atropine. It is a secondary metabolite of some plants, particularly henbane (Hyoscamus niger.)Hyoscyamine is used to provide symptomatic relief to various gastrointestinal disorders including spasms, peptic ulcers, irritable bowel syndrome, pancreatitis, colic and cystitis. It has also been used to relieve some heart problems, control some of the symptoms of Parkinson's disease, as well as for control of respiratory secretions in end of life care [1].
PQCA is a highly selective and potent muscarinic M1 receptor positive allosteric modulator. PQCA has an EC50 value of 49 nM and 135 nM on rhesus and human M1 receptor, respectively, and is inactive for other muscarinic receptors. PQCA improves cognitive performance and cerebral blood flow in rat, cynomolgus macaque, and rhesus macaque. PQCA has potential to reduce the cognitive deficits associated with Alzheimer's disease[1][2].
HY-101653 is a drug with multiple CNS targets, and inhibits acetylcholinesterase (AChE) with Ki of 69 μM; also active against muscarinic M1 and M2 receptors, serotonin 5HT4 receptors, and imidazole I2 receptors.
Gallamine Triethiodide is a synthetic nondepolarizing blocking drug.Target: mAChRGallamine triethiodide is a non-depolarising muscle relaxant. It acts by combining with the cholinergic receptor sites in muscle and competitively blocking the transmitter action of acetylcholine. Gallamine triethiodide has a parasympatholytic effect on the cardiac vagus nerve which causes tachycardia and occasionally hypertension. Very high doses cause histamine release. Gallamine triethiodide is commonly used to stabilize muscle contractions during surgical procedures. From Wikipedia.
Peimisine (Ebeiensine) hydrochloride non-competitively antagonizes tracheal smooth muscle muscarinic M receptor and inhibits smooth muscle contraction caused by Ach. Peimisine hydrochloride excits β-receptor, restrains the release of internal calcium, and promotes to releaseing NO in order to relax tracheal smooth muscle and relieve asthma[1].
DAU 5884 hydrochloride is a potent muscarinic M3 receptor antagonist. DAU 5884 hydrochloride inhibits methacholine-dependent effects on cell proliferation and muscle contractility[1].
Propiverine is a potent antimuscarinic agent. Propiverine inhibits cellular calcium influx, thereby diminishing muscle spasm. Propiverine has neurotropic and musculotropic effects on the urinary bladder smooth muscle. Propiverine can used for overactive bladder (OAB) research[1][2].
N-Demethyl MK-6884 (compound 34) is a potent M4 mAChR allosteric modulator. N-Demethyl MK-6884 can be used in the studies of alzheimer's disease and other diseases mediated by the M4 mAChR[1].
Blarcamesine (AVex-73;AE-37) is an orally bioavailable Sigma-1 receptor agonist and muscarinic receptor modulator, with anticonvulsant, anti-amnesic, neuroprotective and antidepressant properties. Blarcamesine ameliorates neurologic impairments in a mouse model of Rett syndrome[1].