M, receptors

Rezeptor, m. receptor, receiver. Rezeptorenseitenkette, /. receptor sidechain. Rezeptur, /. dispensing (of medicines) recipe ... 

Richardson, B. P., Engel, G., Donatsch, P., and Stadler, P. A. (1985). Identification of serotonin M-receptor subtypes and their specific blockade by a new class of drugs. Nature 316 126-131. 

Ml and M3 receptors mediate the excitatory effects and since this postspike hyperpolarisation is blocked by phorbol esters and is therefore presumably dependent on IP3 production, one would expect it to be mediated through M] receptors (see above), especially as these are located postsynaptically. Unfortunately it does not appear to be affected by pirenzapine, the Mi antagonist. By contrast, muscarinic inhibition of the M current is reduced by the Mi antagonist but as it is not affected by phorbol esters is not likely to be linked to IP3 production, an Mi effect. 

In view of the preponderance of muscarinic receptors in the CNS and the conceived need to augment the muscarinic actions of ACh in the treatment of Alzheimer s disease, much attention has been given recently to the synthesis of agonists that penetrate the blood-brain barrier, especially those that act specifically on M] receptors. 

Tricyclics Preferential inhibition of noradrenaline Imipramine Potent antagonists of M-receptors, i-adrenoceptors... 

Figure 9.2 Autonomic nerve pathways. All preganglionic neurons release acetylcholine (Ach), which binds to nicotinic receptors (N) on the postganglionic neurons. All postganglionic neurons in the parasympathetic system and some sympathetic postganglionic neurons innervating sweat glands release Ach that binds to muscarinic (M) receptors on the cells of the effector tissue. The remaining postganglionic neurons of the sympathetic system release norepinephrine (NE), which binds to alpha (a) or beta (P) receptors on cells of the effector tissue. The cells of the adrenal medulla, which are modified postganglionic neurons in the sympathetic system, release epinephrine (EPI) and NE into the circulation.

Lugli, S.M., Feng, N., Heim, M.H., Adam, M., Schnyder, B., Etter, H., Yamage, M., Eugster, H.P., Lutz, R.A., Zurawski, G. and Moser, R. (1997) Tumor necrosis factor alpha enhances the expression of the interleukin (IL)M receptor alpha-chain on endothelial cells increasing IL-4 or IL-13-induced Stat6 activation. Journal of Biological Chemistry 272, 5487-5494. 

Both nicotinic and muscarinic receptors are widespread in the CNS. Muscarinic receptors with a high affinity for pirenzepine (PZ), M, receptors, predominate in the hippocampus and cerebral cortex, whereas M2 receptors predominate in the cerebellum and brainstem, and M4 receptors are most abundant in the striatum. Central muscarinic and nicotinic receptors are targets of intense pharmacological interest for their potential roles in regulating abnormal neurological signaling in Alzheimer s disease, Parkinson s disease and certain seizure disorders. Nicotinic receptors are largely localized at prejunctional sites and control the release of neurotransmitters [10,11],... 

The 5-HT3 receptor refers to the classical M receptor of Gaddum and Picarelli. Based on its overall electrophysio-logical features and sequence, it is a member of the... 

The biochemistry and pharmacology of 5-HT receptors have been reviewed [74], therapeutic implications presented [75, 76], and functional classification proposed [77], Recently, the neuroanatomy, physiology and pharmacology of 5-HT, receptors have been reviewed [78]. It is evident that major advances have been made since the Gaddum and Picarelli proposal to subdivide 5-HT receptors into D (dibenzyline sensitive) and M (morphine sensitive) types [79]. Subsequently, the D and M receptors have been identified as 5-HT2 and 5-HT, type, respectively. 

Diveu C, Venereau E, Froger J, et al Molecular and functional characterization of a soluble form of oncostatin M/interleukin-31 shared receptor. J Biol Chem 2006 281 36673-36682. Stress C, Radtke S, Clahsen T, et al Oncostatin M receptor-mediated signal transduction is negatively regulated by SOCS3 through a receptor tyrosine-independent mechanism. J Biol Chem 2006 281 8458-8468. 

Gastric secretion. Stimulation of gastric acid production by vagal impulses involves an M-cholinoceptor subtype (M -receptor), probably associated with enterochromaffin cells. Pirenzepine (p. 106) displays a preferential affinity for this receptor subtype. Remarkably, the HCl-secreting parietal cells possess only Ma-receptors. Mi-receptors have also been demonstrated in the brain however, these cannot be reached by pirenzepine because its lipophilicity is too low to permit penetration of the blood-brain barrier. Pirenzepine was formerly used in the treatment of gastric and duodenal ulcers (p. 166). 

The snbgronps of muscarinic receptors (Mj and M2) are activated or blocked by various substances however, both types of muscarinic receptors are activated by an endogenic nenrotransmitter—acetylcholine—and are blocked by atropine or scopolamine. Despite the fact that atropine and scopolamine are reversible cholinoblocking agents, the constants of their dissociation with M-receptors are several times less than acetylcholine. Accordingly, their action is more prolonged (for a few days). 

Belladonna alkaloids have an extremely broad pharmacological spectrum. In addition to their ability to block M-receptors, atropine and scopolamine also act on other receptors, thus showing corresponding effects. They can only block nicotinic cholinergic receptors, however, in significantly larger doses than those used in clinics. Atropine also exhibits properties of local anesthetics and histamine (Hj) receptor blockers. Atropine and... 

Affinity for M receptor and analgesic activity in vivo (mice) 0.45 0.40... 

Vincent, J.P., Vignon, J., Kartalovski, B., and Lazdunski, M. Receptor sites for phencyclidine in mammalian brain and peripheral organs. In Domino, E.F., ed. PCP (Phencyclidine) Historical and Current Perspectives. Ann Arbor, MI. NPP Books. 1981. p. 83-103. 

Muscarinic M3 Exocrine glands, vessels (smooth muscle and endothelium) CNS neurons Like M receptor-ligand binding... 

Lamping KG et al Muscarinic (M) receptors in coronary circulation. Arterioscler Thromb Vase Biol 2004 24 1253. [PMID 15130910]... 

Ipratropium Competitive, nonselective antagonist at M receptors Reduces or prevents bronchospasm Prevention and relief of acute episodes of bronchospasm Aerosol canister, up to qid Toxicity Xerostomia, cough Interactions With other antimuscarinics... 

Benztropine Antagonist at M receptors in basal ganglia Reduces tremor and rigidity little effect on bradykinesia Parkinson s disease Oral Toxicity Typical antimuscarinic effects sedation, mydriasis, urinary retention, dry mouth... 

Chlorpromazine Blockade of D2 receptors >> 5 2 receptors .-Receptor blockade (fluphenazine least) muscarinic (M)-receptor blockade (especially chlorpromazine and thioridazine) Hx-receptor blockade (chlorpromazine, thiothixene) t central nervous system (CNS) depression (sedation) t decreased seizure threshold t QT prolongation (thioridazine) Psychiatric schizophrenia (alleviate positive symptoms), bipolar disorder (manic phase) nonpsychiatric antiemesis, preoperative sedation (promethazine) pruritus Oral and parenteral forms, long half-lives with metabolism-dependent elimination Toxicity Extensions of effects on a - and M- receptors blockade of dopamine receptors may result in akathisia, dystonia, parkinsonian symptoms, tardivedyskinesia, and hyperprolactinemia... 

Haloperidol Blockade of D2 receptors >> 5HT2A receptors Some a blockade, but minimal M receptor blockade and much less sedation than the phenothiazines Schizophrenia (alleviates positive symptoms), bipolar disorder (manic phase), Huntington s chorea, Tourette s syndrome Oral and parenteral forms with metabolism-dependent elimination Toxicity Extrapyramidal dysfunction is major adverse effect... 

Aripiprazole Blockade of 5HT2A receptors > blockade of D2 receptors Some a blockade (clozapine, risperidone, ziprasidone) and M-receptor blockade (clozapine, olanzapine) variable receptor blockade (all) Schizophrenia—improve both positive and negative symptoms bipolar disorder (olanzapine or risperidone adjunctive with lithium) agitation in Alzheimer s and Parkinson s (low doses) major depression (aripiprazole) Toxicity Agranulocytosis (clozapine), diabetes (clozapine, olanzapine), hypercholesterolemia (clozapine, olanzapine), hyperprolactinemia (risperidone), QT prolongation (ziprasidone), weight gain (clozapine, olanzapine)... 

The novel use of J-receptor antagonists with M-receptor agonists is also emerging as a strategy to avoid the development of tolerance. This idea has developed around the observation that mice lacking the J-opioid receptor fail to develop tolerance to morphine. 

The concurrent administration of methadone to heroin addicts known to be recidivists has been questioned because of the increased risk of overdose death secondary to respiratory arrest. Buprenorphine, a partial M-receptor agonist with long-acting properties, has been found to be effective in opioid detoxification and maintenance programs and is presumably associated with a lower risk of such overdose fatalities. 

Butorphanol produces analgesia equivalent to nalbuphine and buprenorphine but appears to produce more sedation at equianalgesic doses. Butorphanol is considered to be predominantly agonist. However, it may also act as a partial agonist or antagonist at the M- receptor. 

The receptor 67 [54] shows the sensing of F in DMSO. Upon addition of F to the solution of receptor 67 two bands at 323 and 525 nm decreased and a new band at 652 nm appeared. Furthermore, the color of the solution changed from red-pink to pale purple. These spectral changes were ascribed to the formation of a 1 1 adduct between the metal complex and F anion, in which F anion bound two dipyrrolylquinoxaline units (fC=54,000 M ) Receptor 67 was also studied electrochemically by cyclic voltammetry. A clearly reversible redox signal was observed at 160 mV (vs SHE), which was assigned to the Co(III)/Co(II) reduction. The addition of F led to a complete disappearance... 

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