Neuromuscular action

Neomycin is particularly ototoxic and nephrotoxic when given parenterally. As with gentamicin and kanamycin, the nephrotoxicity may be reversible but the ototoxicity is usually irreversible and deafness may occur following oral administration, instillation into cavities, or topical use. It may block neuromuscular action and respiratory depression has been reported. Local treatments may cause hypersensitivity, rashes, pruritus, and anaphylaxis. Neomycin is not geno-toxic. 

Alkaloids which activate neuromuscular action (so-called parasympa-thomimetics) include nicotine, arecoline, physostigmine, coniine, cytisine, and sparteine. Inhibitory (or parasympatholytic) alkaloids include hyoscy-amine and scopolamine, (see above) 312). Skeletal muscles as well as muscle-containing organs, such as lungs, heart, circulatory system, and gut, and the nervous system are certainly very critical targets. The compounds are usually considered to be strong poisons, and it is obvious that... 

Since AN binds the nicotinic acetylcholine receptor irreversibly, this toxin is useful for studying this receptor as well as the mechanisms of neuromuscular action. Analogues of AN have been used to study the receptor subtypes, and important research goals are the development of new drag... 

Maeda, M., Kodama, T, Saito, M., Tanaka, T, Yoshizumi, H., Nomoto, K., and Fujita, T. 1987a. Neuromuscular action of insecticidal domoic acid on the American cockroach. Pesticide Biochemistry and Physiology 28, 85-92. 

Rickett, D.L., Glenn, J.F., Beers, E.T. (1986). Central respiratory effects versus neuromuscular actions of nerve agents. Neurotoxicology 1 225—36. 

Furosemide (40-80 mg) has been reported to enhance and prolong D-tubocurarine-induced block in anephric patients (63). In animals low doses potentiated D-tubocur-arine (and suxamethonium) probably via presynaptic effects, while high doses (1-40 mg/kg in cats) reversed the neuromuscular actions of these relaxants (64). The effects of high doses were similar to those of theophylline. 

Rickett, D, L. (1981, June 8-9). Soman produced respirator) arrest Differentiation of brain stem and neuromuscular action.s. USAMRDC Cheni Prog. Rev. [abstract],... 

Ojewole JAO, Adesina SK 1983 Cardiovascular and neuromuscular actions of scopoletin from fruit of Tetrapleura tetraptera. Planta Med 49 99-102... 

Lujan, J.L. and Crago, RE. 2009. Automated optimal coordination of multiple-DOF neuromuscular actions in feedforward neuroprostheses. lEEE-TBME, 56(1) 179-187. 

Mode of Action. All of the insecticidal carbamates are cholinergic, and poisoned insects and mammals exhibit violent convulsions and other neuromuscular disturbances. The insecticides are strong carbamylating inhibitors of acetylcholinesterase and may also have a direct action on the acetylcholine receptors because of their pronounced stmctural resemblance to acetylcholine. The overall mechanism for carbamate interaction with acetylcholinesterase is analogous to the normal three-step hydrolysis of acetylcholine however, is much slower than with the acetylated enzyme. 

Isoflurane is a respiratory depressant (71). At concentrations which are associated with surgical levels of anesthesia, there is Htde or no depression of myocardial function. In experimental animals, isoflurane is the safest of the oral clinical agents (72). Cardiac output is maintained despite a decrease in stroke volume. This is usually because of an increase in heart rate. The decrease in blood pressure can be used to produce "deHberate hypotension" necessary for some intracranial procedures (73). This agent produces less sensitization of the human heart to epinephrine relative to the other inhaled anesthetics. Isoflurane potentiates the action of neuromuscular blockers and when used alone can produce sufficient muscle relaxation (74). Of all the inhaled agents currently in use, isoflurane is metabolized to the least extent (75). Unlike halothane, isoflurane does not appear to produce Hver injury and unlike methoxyflurane, isoflurane is not associated with renal toxicity. 

Neuromuscular junction (NMJ) is the synapse or junction of the axon terminal of motoneurons with the highly excitable region of the muscle fibre s plasma membrane. Neuronal signals pass through the NMJ via the neurotransmitter ACh. Consequent initiation of action potentials across the muscle s cell surface ultimately causes the muscle contraction. 

It is important to use these drag with caution in patients with a history of gastrointestinal disorders, renal disease, or liver impairment. The neuromuscular blocking action of die lincosamides poses a danger to patients widi myasthenia gravis (an autoimmune disease manifested by extreme weakness and exhaustion of die muscles). 

When kaolin or aluminum is administered widi die lincosamides, die absorption of the lincosamide is decreased. When the lincosamides are administered with the neuromuscular blocking drag (drag diat are used as adjuncts to anesthetic drag diat cause paralysis of the respiratory system) die action of die neuromuscular blocking drug is enhanced, possibly leading to severe and profound respiratory depression. 

As distinct from the acetyl choline receptor of the neuromuscular junction, the acetyl receptors of the viscera are not blocked by nicotine but are blocked by muscarine. Moreover, based on differences in the binding of the muscarinic antagonist, pirenzapine, the muscarinic acetyl choline receptors (mAChRs), are separated into two classes, viz. high affinity mj receptors, and low affinity m2 receptors. The latter predominates in the heart, cerebellum, and smooth muscle broadly. These different receptors mediate quite different actions. 

Voluntary muscle contraction is initiated in the brain-eliciting action potentials which are transmitted via motor nerves to the neuromuscular junction where acetylcholine is released causing a depolarization of the muscle cell membrane. An action potential is formed which is spread over the surface membrane and into the transverse (T) tubular system. The action potential in the T-tubular system triggers Ca " release from the sarcoplasmic reticulum (SR) into the myoplasm where Ca " binds to troponin C and activates actin. This results in crossbridge formation between actin and myosin and muscle contraction. 

Another possible target for toxins are the receptors for neurotransmitters since such receptors are vital, especially for locomotion. In vertebrates the most strategic receptor is that for acetylcholine, the nicotinic receptor. In view of the breadth of action of the various conotoxins it is perhaps not surprising that alpha-conotoxin binds selectively to the nicotinic receptor. It is entirely possible that similar blockers exist for the receptors which are vital to locomotion in lower species. As mentioned previously, lophotoxin effects vertebrate neuromuscular junctions. It appears to act on the end plate region of skeletal muscle (79,59), to block the nicotinic receptor at a site different from the binding sites for other blockers (81). 

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