Acetylcholine receptors blockers

Heidmann, T. Oswald, R.E. and Changeux, J.-P. Multiple sites of action for noncompetitive blockers on acetylcholine receptor rich membrane fragments from Torpedo marmorata. Biochemistry 22 3112-3127, 1983. 

Neuromuscular - mild stimulation to muscle paralysis, respiratory failure (curare), death Tobacco -South American -Strychnos family (curare) Blue green alga (anatonin A) Nicotine - blocks acetylcholine receptors Curare - used as a hunting poison, very potent receptor blocker... 

D2-receptor blocker removes inhibition of acetylcholine neurons in enteric nervous system... 

Buisson B. and Bertrand D. (1998). Open-channel blockers at the human a4/32 neuronal nicotinic acetylcholine receptor. Mol. Pharmacol. 53 555-563. 

Bahr BA, Parsons SM (1986) Demonstration of a receptor in Torpedo synaptic vesicles for the acetylcholine storage blocker L-trans-2-(4-phenyl[3,4-3H]-piperidino)cyclohexanol. Proc Natl Acad Sci USA 83 2267-2270. 

Magdesian MH, Nery AA, Martins AH, Juliano MA, Juliano L, Uhich H, Ferreira ST (2005) Peptide blockers of the inhibition of neuronal nicotinic acetylcholine receptors by amyloid beta. J Biol Chem 280 31085-31090... 

For the selective labeling of the acetylcholine receptor Saitoh et al. used the covalently bound non-competitive blocker 5-azido- H-trimethioquin. Asymmetric labeling of the proteins in the kidney microvillar membrane by lactoperoxidase-catalysed radioiodination and by photolysis of 3,5-di- I-4-azidobenzenesulphonate is a new approach which may be applied to the topological investigation of ojmplex membranes... 

KYNA acts both, as a blocker of the glycine coagonistic site of the NMDA receptor (Kessler et al., 1989) and as a non-competitive inhibitor of the a7 nicotinic acetylcholine receptor (Hilmas et al., 2001). 

Action on receptors provides numerous examples. Beneficial interactions are sought in overdose, as with the use of naloxone for morphine overdose (opioid receptor), of atropine for anticholinesterase, i.e. insecticide poisoning (acetylcholine receptor), of isoproterelol (isoprenaline) for overdose with a P-adrenoceptor blocker (p-adrenoceptor), of phentolamine for the monoamine oxidase inhibitor-sympathomimetic interaction (a-adrenoceptor). 

Martyn JA, White DA, Gronert GA, Jaffe RS, Ward JM. Up-and-down regnlation of skeletal muscle acetylcholine receptors. Effects on nenromuscular blockers. Anesthesiology 1992 76(5) 822-43. 

Ipratropium bromide is a nonselective muscarinic receptor blocker, and blockade of inhibitory muscarinic receptors theoretically could result in an increased release of acetylcholine and overcome the block on the smooth muscle receptors (M3). Oifly the quaternary ammonium derivatives such as ipratropium bromide should be used because they have the advantage of poor absorption across mucosae and the blood-brain barrier. This results in negligible systemic effects with a prolonged local effect (i.e., bronchodilation). In addition, the quaternary compounds do not appear to produce a decrease in mucocfliary clearance. Ipratropium bromide has a duration of action of 4 to 8 hours. Both intensity and duration of action are dose-dependent. Time to reach maximum bronchodilation is considerably slower than from aerosolized short-acting 82-agonists (2 hours versus 30 minutes). However, this is of little clinical consequence because some bronchodilation is seen within 30 seconds, 50% of maximum response occurs within 3 minutes, and 80% of maximum is reached within 30 minutes. Ipratropium bromide is oifly indicated as adjunctive therapy in severe acute asthma not completely responsive to 82-agonists alone because it does not improve outcomes in chronic asthma. ... 

Several studies employing oocytes of the clawed frog, Xenopus laevis, for the in vitro translation of sodium channel encoding mRNAs (53-55) suggest that this experimental system may be particularly useful toward this end. The biophysical properties of sodium channels expressed in oocytes following injection of rat brain mRNA were similar to those of sodium channels in their native membrane environment, and were specifically inhibited by the sodium channel blockers tetrodotoxin and saxitoxin (i5.). Sodium channels encoded by mRNAs from rat skeletal muscle and eel electroplax have also been expressed in Xenopus oocytes (56-57). To date the expression of insect sodium channels in the Xenopus oocyte has not been reported, but the utility of this system for the translation and expression of insect acetylcholine receptor mRNA has recently been demonstrated (58). Successful application of this methodology to the expression of insect mRNAs encoding functional sodium channels offers a novel method to test some of the hypotheses for the molecular basis of the kdr mechanism. 

Synthesis of poison frog alkaloids as novel, potent, and subtype-selective blockers of neuronal nicotinic acetylcholine receptors 06Y49. 

All local anaesthetics have some neuromuscular blocking activity and may enhance the block produced by competitive neuromuscular blockers if given in sufficient doses. Procainamide also has acetylcholine receptor channel blocking activity. ... 

A series of potent alkaloids were first isolated from den-drobatid frogs of western Colombia and northwestern Ecuador, but are now known to be more widespread in distribution. These alkaloids affect at least three classes of channels in nerve and muscle. The first two are receptor-regulated channels, in particular the nicotinic acetylcholine receptor channel. The histrionicotoxins are noncompetitive blockers of this receptor-channel complex (Daly et al, 1993). The second class of channels are the voltage-dependent sodium channels. Histrionicotoxins reduce conductances in a manner reminiscent of local anesthetics (Daly et al., 1993). Despite these effects, these alkaloids have relatively low toxicity (Daly et al., 1993). 

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