Thiochrome, a natural oxidation product and metabolite of thiamine, is a selective M4 muscarinic receptor of acetylcholine (ACh) affinity enhancer. Thiochrome has neutral cooperativity with ACh at M1 to M3 receptors[1][2].
Penehyclidine, a anticholinergic agent, is a selective antagonist of M1 and M3 receptors. Penehyclidine activates NF-kβ in lung tissue and inhibits the release of inflammatory factors. Penehyclidine can alleviate the pulmonary inflammatory response in rats with chronic obstructive pulmonary disease (COPD) undergoing mechanical ventilation[1][2].
Clozapine D8 (HF 1854 D8) is the deuterium labeled Clozapine. Clozapine, an antipsychotic, is a potent antagonist of dopamine and a number of other receptors, with a Ki of 9.5 nM for muscarinic M1 receptor. Clozapine is also a potent and selective agonist at the muscarinic M4 receptor (EC50=11 nM)[1][2][3][4].
(±)-Darifenacin-d4 (hydrobromide) is deuterium labeled (±)-Darifenacin. (±)-Darifenacin is the racemate of Darifenacin. Darifenacin is a selective M3 muscarinic receptor antagonist[1].
(Rac)-5-Hydroxymethyl Tolterodine ((Rac)-Desfesoterodine), an active metabolite of Tolterodine, is a mAChR antagonist (Ki values of 2.3 nM, 2 nM, 2.5 nM, 2.8 nM, and 2.9 nM for M1, M2, M3, M4, and M5 receptors, respectively). (Rac)-5-Hydroxymethyl Tolterodine can be used for overactive bladder research[1].
BIBN-99 is a selective, BBB-penetrable and competitive muscarinic M2 receptor antagonist. BIBN-99 improves cognitive performancein rats with traumatic brain injury[1][2].
Tolterodine-d14 (hydrochloride) is the deuterium labeled Tolterodine hydrochloride[1]. Tolterodine hydrochloride is a potent muscarinic receptor antagonist[2][3].
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
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].
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].
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].
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].
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].
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.
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].
Pirenzepine dihydrochloride (LS519) is a selective M1 muscarinic receptor antagonist.
Scopolamine is a high affinity (nM) muscarinic antagonist. 5-HT3 receptor-responses are reversibly inhibited by Scopolamine with an IC50 of 2.09 μM.
Cevimeline (Evoxac) is a parasympathomimetic and muscarinic agonist, with particular effect on M3 receptors; used in the treatment of dry mouth associated with sjogren's syndrome.IC50 value:Target: M3 receptor
Sabcomeline (hydrochloride) is a potent and functionally selective muscarinic M1 receptor partial agonist that improve cognition.
Atropine (Tropine tropate) hydrobromide is a competitive muscarinic acetylcholine receptor (mAChR) antagonist with IC50 values of 0.39 and 0.71 nM for Human mAChR M4 and Chicken mAChR M4, respectively. Atropine hydrobromide inhibits ACh-induced relaxations in human pulmonary veins. Atropine hydrobromide can be used for research of anti-myopia and bradycardia[1][2][3][4].
Clozapine N-oxide (CNO) is a major metabolite of the anti-psychotic drug clozapine. Clozapine N-oxide is a agonist for the chemogenetic Designer Receptors Exclusively Activated by Designer Drug (DREADD) system.
W-84 (dibromide) is a potent allosteric modulator of M2-cholinoceptors, which retards [3H]N-methylscopolamine dissociation. W-84 dibromide can stabilize cholinergic antagonist-receptor complexes. W-84 (dibromide) is a non-competitive muscarinic acetylcholine receptors antagonist with allosteric effects. W-84 (dibromide) protects over additively against an organophosphate-intoxication when applied in combination with atropine[1][2][3].
Prifinium bromide is antimuscarinic agent with antispasmodic, antiemetic effect[1].
Methylbenactyzium Bromide is a muscarinic acetylcholine receptor (mAChR) inhibitor.
Nor-benzetimide is a major metabolite of Benzetimide. Benzetimide is a mAChR antagonist with anticholinergic activity[1][2].
Xanomeline, as an effective and selective muscarinic type 1 and type 4 (M1/M4) receptor agonist, increases neuronal excitability. Xanomeline can be used for the research of neurological disorders, such as schizophrenia[1][2].