Muscarinic Ml receptor

Fanelli, F., Menziani, M.C., Carotti, A. and De Benedetti, P.G. (1994) Theoretical quantitative structure-activity relationship analysis on three dimensional models of ligand-ml muscarinic receptor complexes. Bioorganic S. Medicinal Chemistry, 2, 195-211. 

Metabotropic G-protein linked receptors are also modulated by general anesthetics. In particular, the current produced through activation of muscarinic receptors (Ml) for acetylcholine and the serotonergic receptor 5HT2 is inhibited by halothane, isoflurane and enflurane (Lin et al., 1993 Minami et al., 1994 Durieux, 1995). Ketamine inhibits muscarinic receptors although there is no stereospecificity of inhibition (Durieux Nietgen, 1997). The S-isomer of ketamine is more potent as an anesthetic than the R-isomer (Benthuysen et al., 1989). It is thus unlikely that the Ml muscarinic receptor plays a role in... 

Lechner SG, Mayer M, Boehm S (2003) Activation of Ml muscarinic receptors triggers transmitter release from rat sympathetic neurons through an inhibition of M-type K+ channels. J Physiol... 

Liu L, Zhao R, Bai Y, Stanish LF, Evans JE, Sanderson MJ, Bonventre JV, Rittenhouse AR (2006) Ml muscarinic receptors inhibit L-type Ca2+ current and M-current by divergent signal transduction cascades. J Neurosci 26 11588-98... 

Weiner DM, Meltzer HY, Veinbergs I, Donohue EM, Spalding TA, et al. 2004. The role of Ml muscarinic receptor agonism of N-desmethylclozapine in the unique clinical effects of clozapine. Psychopharmacology 177 207-216. 

ACh interneurons interact with the dopaminergic system in several ways. Dopamine-dependent long-term potentiation (LTD) is mediated by D2 receptors (in the indirect pathway) but D2 receptors are also reported on cholinergic interneurons. Acetylcholine release activates mainly through Ml muscarinic receptors at glutamatergic axo-spinous synapses (Hersch et al., 1994). 

Payette, P. Gossard, F. Whiteway, M. Dermis, M. Expression and pharmacological characterization of the human Ml muscarinic receptor in saccharomyces cerevi- 50. siae. FEBS Lett. 1990, 266, 21-25. 

Mistry SN, Valant C, Sexton PM, Capuano B, Christopoulos A, Scammells PJ (2013) Synthesis and pharmacological profiling of analogues of benzyl quinolone carboxylic acid (BQCA) as allosteric modulators of the Ml muscarinic receptor. J Med Chem 56 5151-5172... 

Usually chiral centers are eliminated in creating symmetry. Thus, in a series of muscarinic agonists derived from 3-aminopyridazines, one of the most favorable side-chains, was the racemic 2-Ai-ethylpyrroMmyl-methyl chain, that is, the side-chain of sulpiride (Figure 26.8). The 5-methyl-6-phenylpyridazine bearing this basic chain at its 3-amino function presented a 0.26 micromolar affinity for Ml muscarinic receptor preparations. ... 

Wang, S. Z., Hu, J. R Long. R. M, Pou. W. S., Forray. C, and el-Fakahany, E. E. (1990). Agonist-induced down-regulation of ml muscarinic receptors and reduction of their raRNA level in a transfected cell line. FEBS Lett. 276, 185-188. 

Acetylcholine is stored in storage vesicles. 3). Upon nerve stimulation, an action potential travels down the neuron and causes calcium influx into the nerve terminal. Calcium influx causes the vesicles to fuse with plasma membrane and release acetylcholine. Acetylcholine diffuses through the synaptic cleft and may bind to (4) Nm receptors (nicotinic receptors on muscle cells, (5) Ng receptors (nicotinic receptors on ganglionic synapses of the autonomic nervous system), (6) Ml muscarinic receptors, (7) M2 muscarinic receptors or (8) M3 muscarinic receptors. At least six muscarinic receptors have now been identified, of which Ml, M2 and M3 receptors have been most carefully studied (Table 2.5). 

Fig. 39.2 Suggested effects leading to neuroprotective activity of hupA in AD. HupA is considered to modulate the APP processing by inducing the activity of a-secretase. The increased activity of a-secretase causes enhancement of nutritional APP (sAPPa) and consequently inhibition the A[i pathway. These APP-modulating effects are mediated through Ml muscarinic receptor-mediated PKC-dependent cascade and Trk receptor-mediated ERK/MAPK-dependent cascade and caused by increased levels of ACh and NGF in the synaptic junction. Increased release of sAPPa and decreased A(3 release from APP followed by inhibition of A[i fibril formations affects the regulation of the expression of apoptotic proteins, attenuates oxidative stress, and allows the mitochondria, respiratory chain, and TCA cycle to function normally. APP amyloid precursor protein, PKC protein kinase C. ERK extracellular signal-regulating kinase, MAPK mitogen-activated protein kinase, TCA tricarboxylic acid cycle (citric acid cycle)...

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