Disease relevance of Lopac-C-7041

• 4. Low concentrations (1-2 microM) of muscarine, carbachol, oxotremorine or the muscarinic ganglion stimulant, McN-A-343 (1-10 microM) reduced the a.h.p. current and leak conductance and induced a steady inward current, without affecting M-current (IM) relaxations [1].
• Abolition of McN-A-343-induced emesis only occurred with the largest dose of atropine (1 mg) [2].
• 4. McN-A-343-induced tachycardia was also the result of muscarinic receptor activation [3].
• The low sensitivity of the neostigmine-induced bradycardia to pirenzepine, and the failure of McN-A-343 to evoke bradycardia, suggest the receptor on cardiac ganglion cells is not an M1-type.(ABSTRACT TRUNCATED AT 250 WORDS)[4]
• 1. Intravenous injection of the muscarinic agonist, McN-A-343, in conscious dogs equipped with an ileal Thiry fistula produced a dose-related inhibition of intestinal phasic contractile activity, and an increase in heart rate [3].

Psychiatry related information on Lopac-C-7041

• Bilateral perfusion with either McN-A-343 (M1 muscarinic) or nicotine (both 10(-5)-10(-3) M) did not have any effect on cataplexy in either narcoleptic or control canines [5].
• 1. The ability to modify the pain threshold by the two M1-muscarinic agonists: McN-A-343 and AF-102B and by the specific M2-agonist arecaidine was examined in mice and rats by using three different noxious stimuli: chemical (writhing test), thermic (hot-plate test) and mechanical (paw pressure test) [6].
• The M1 agonist McN-A-343 did not elicit any change in sleep or REM sleep percentage [7].
• On trial 2 in the elevated plus-maze, a model of specific phobia, the endogenous cholinergic system, nicotine, and the M(1) receptor agonist, McN-A-343, all mediate an anxiolytic effect, whereas stimulation of 5-HT(1A) receptors mediates an anxiogenic effect [8].

High impact information on Lopac-C-7041

• Moreover, 4-(m-chlorophenyl carbamoyloxy)-2-butyltrimethylammonium chloride (McN-A-343), a muscarinic ganglionic stimulant, also caused relaxation of the lower esophageal sphincter [9].
• In rabbit vas deferens, the inhibitory effect of the combination of C7/3-phth and atropine on the responses to McN-A-343 at the M1 receptor was more pronounced than that of the combination of C7/3-phth and PZP [10].
• Selectivity of McN-A-343 in stimulating phosphoinositide hydrolysis mediated by M1 muscarinic receptors [11].
• In addition, microinjection of ACh (5 pmol) or the muscarinic M1 receptor agonist McN-A-343 (30 ng) into the lateral hypothalamic nucleus increased pancreatic secretion over basal levels by 46 % and 40 %, respectively [12].
• Islet-activating protein (2 micrograms/2 microliters) treatment alone did not change in vivo striatal dopamine (DA) release and metabolism, but completely abolished the increase of striatal DA release evoked in vivo by the M1-selective agonist McN-A-343 (10(-7) M) [13].

Chemical compound and disease context of Lopac-C-7041

• Propranolol partially reduced McN-A-343 tachycardia, suggesting catecholamine release [3].
• In addition, the mechanical hypersensitivity in diabetic mice was reduced by the selective muscarinic M1 receptor agonist McN-A-343 (4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium chloride) (i.t.). These results suggest that spinal muscarinic M1 receptors participate in the antiallodynic effect of clonidine in diabetic mice [14].
• The dose of PZP used blocked the increase in FLPP and HR evoked by the muscarinic receptor agonist McN-A-343, but not the increase evoked by the nicotinic receptor agonist DMPP, when these drugs were injected into the arterial supply of the ganglion [15].
• 3. Doses of guanethidine (1 mg/kg) and pentacynium (1 mg/kg) blocking pressor responses to intravenous administration of the ganglion stimulants McN-A-343 and DMPP, respectively, did not affect responses to AA [16].

Biological context of Lopac-C-7041

• Pharmacological characterization of muscarinic receptors involved in McN-A-343-induced effects on intestinal motility and heart rate in conscious dogs [3].
• Vasoactive intestinal polypeptide (0.075-1.5 nmol) unmasked the muscarinic slow negative potential, following the compound action potential and unmasked or enhanced the stimulus-bound decremental oscillatory potentials induced by the muscarinic agonist McN-A-343 in the superior cervical ganglion [17].
• Treatment with McN-A-343, 100-1000 micrograms/site, did not alter blood pressure, heart rate or renal sympathetic nerve discharges [18].
• McN-A-343 was not selective in terms of affinity since its dissociation constants at M1 and M2 binding sites in the rat cerebral cortex and myocardium respectively, were very similar (cortical pPKi = 5.05; myocardial pKi = 5.22) [19].
• 4-[[N-(3-Chlorophenyl)-carbamoyl]oxy]-2-butynyltrimethylammonium chloride (McN-A-343) and N-ethyl-guvacine propargyl ester (NEN-APE) produced minimal or no arteriolar vasodilation [20].

Anatomical context of Lopac-C-7041

• The aziridinium ion had 1/4 the potency of McN-A-343 (1) as a ganglionic muscarinic stimulant in the anesthetized, pentolinium-treated rat but showed no muscarinic effects on the isolated guinea pig ileum [21].
• Two M1-mediated responses elicited by McN-A-343 were studied: relaxation of the isolated rat duodenum and inhibition of twitch contractions in rabbit was deferens [22].
• The effect of McN-A-343 on muscarinic receptors in the cerebral cortex and heart [23].
• The M1-selective compound, pirenzepine (1-30 micrograms kg-1), was a potent antagonist of the McN-A-343 effect, whereas the cardioselective M2-antagonist, AF-DX 116, and the smooth muscle selective compound, 4-diphenylacetoxy-N-methyl piperidine (4-DAMP), were completely ineffective at the doses tested [3].
• It is postulated that the emesis produced by McN-A-343, injected into the cerebral ventricles, is mediated through muscarinic M1 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)[2]

Associations of Lopac-C-7041 with other chemical compounds

• The nonselective muscarinic receptor agonists muscarine and carbachol both stimulated alphaMSH release from perifused frog NILs, whereas the M1-selective muscarinic agonist McN-A-343 was virtually devoid of effect [24].
• A comparison was made with the affinity of McN-A-343 as an antagonist (KB) of acetylcholine-induced contraction in rat duodenum [22].
• The subtype selectivity of pilocarpine and McN-A-343 in these cases was not due to differences in the level of expression of muscarinic receptors in the various cell lines [25].
• While oxotremorine reduced the release of [3H]acetylcholine and [3H]-noradrenaline in a concentration-dependent manner from different release sites (Auerbach plexus, noradrenergic neurons in the right atrium, cerebral cortex), McN-A 343, an M1 receptor agonist, enhanced their release evoked by field stimulation [26].
• 2. In the immature guinea-pig assay, the responses to 5-MeF and McN-A 343 were abolished by histamine H2-receptor blockade suggesting that the responses were totally dependent upon gastric mucosal histamine [27].

Gene context of Lopac-C-7041

• ACh and McN-A-343 produced endothelium-dependent dilation that was blocked by 4-diphenyl-N-methyl-piperidine methiodide, an inhibitor of the M3 receptor [28].
• Pharmacological characterization of the MAPK response revealed that McN-A-343 was a partial agonist at the M1 and M3 subtypes, and that pilocarpine was a partial agonist at the M3 and M5 receptors [29].
• Forskolin (10(-5) M), an adenylate cyclase activator, increased DA release and showed an additive effect on the DA release evoked by McN-A-343 [13].
• METHOD: Anxiety was evaluated in the elevated plusmaze and spontaneous working memory was evaluated in the Y-maze following scopolamine, pirenzepine or McN-A-343 infusion in the IL cortex [30].
• 1. Concentration-effect curves were obtained, in the absence and presence of histamine H2-receptor blockade, to 5-methylfurmethide (5-MeF) and McN-A 343, high efficacy and low efficacy acetylcholine (ACh) M-receptor agonists, respectively, in isolated stomach preparations from the mouse and immature rat and guinea-pig [27].

Analytical, diagnostic and therapeutic context of Lopac-C-7041

• Topical McN-A-343 (10(-7), 10(-4) M), an M-1 agonist, produced pial arteriolar constriction (diameters were 140 +/- 8, 127 +/- 9 and 111 +/- 8 microns for control, 10(-7) and 10(-4) M McN-A-343) that was blocked by topical pirenzepine (10(-3) M), an M-1 antagonist [31].
• 3 Close intra-arterial injection of SGTX (6.2-12.3 nmol/kg) to the superior cervical ganglion blocked the contractile response of the nictitating membrane to preganglionic stimulation of cervical sympathetic nerve or injected DMPP, but not to postganglionic stimulation or to injected adrenaline and McN-A-343 [32].
• Pressure application of McN-A-343 onto isolated DUM neurones induced a dose- and voltage-dependent biphasic response composed of a fast initial hyperpolarization followed by a slow depolarizing phase, recorded with the patch-clamp technique in the whole-cell recording configuration [33].
• 3. Pressor responses elicited either by electrical stimulation of the spinal sympathetic outflow or by stimulation of sympathetic ganglion cells with the muscarinic agonist McN-A-343 were reduced by DAMA [34].
• Using the cannula inserting method, we investigated vascular responses to ACh and McN-A-343 (a M1-agonist) in isolated and perfused canine and simian facial veins in non-preconstricted conditions [35].

References