Muscle relaxant effects

Neuromuscular Nicotinic receptors are responsible for transmission at the neuromuscular junction. While briefly causing stimulation, this phase is rapidly obscured by desensitization and neuromuscular blockade. Thus, nicotine has muscle-relaxant effects. 

Halothane exerts a pronounced hypotensive effect, to which a negative inotropic effect contributes. Enflurane and isoflurane cause less circulatory depression. Halothane sensitizes the myocardium to catecholamines (caution serious tachyarrhythmias or ventricular fibrillation may accompany use of catecholamines as antihypotensives or toco-lytics). This effect is much less pronounced with enflurane and isoflurane. Unlike halothane, enflurane and isoflurane have a muscle-relaxant effect that is additive with that of nondepolarizing neuromuscular blockers. 

In surgical practice, two barbiturates are primarily used thiopental and methohexital. However, it should be stated that barbiturates are hypnotics, and at therapeutic doses has a very weak analgesic and muscle relaxant effect, which general anesthetics must possess. 

Phentolamine is also a derivative of imidazoline that exhibits a direct a-adrenoblocking, muscle-relaxant effect on smooth muscle as well as cholinomimetic, histamine, and sympathomimetic effects. The chemical variation of its stmcture permits a few of its properties to be more expressed. For example, the aforementioned tolazoline, 2-benzyl-2-imidazoline, a structural analog of phentolamine, has more of an expressed muscle-relaxant effect on smooth muscle than an a-adrenoblocking effect. 

Pharmacology Mechanism of action is unknown. It differs from benzodiazepines in that it does not exert anticonvulsant or muscle relaxant effects. It also lacks prominent sedative effects associated with more typical anxiolytics. Buspirone has effects on serotonin, dopamine, and norephinephrine. 

Nitrous oxide is the only inhalation anesthetic that is a gas. It is chemically inert. Nitrous oxide has little effect on overall cardiovascular function. Disadvantages are that it has no muscle relaxing effect and that it cannot be used on its own because of high Minimal Alveolar Concentration values needed for adequate anesthesia. During recovery there is a risk for hypoxia and anesthesia should be slowly tapered off to prevent this event. 

Nonselective antimuscarinic drugs have been employed in the therapy of peptic ulcers (see Chapter 40) because they can reduce gastric acid secretion they also have been used as adjunctive therapy in the treatment of irritable bowel syndrome. Antimuscarinic drugs can decrease the pain associated with postprandial spasm of intestinal smooth muscle by blocking contractile responses to ACh. Some of the agents used for this disorder have only antimuscarinic activity (e.g., propantheline), while other drugs have additional properties that contribute to their antispasmodic action. Dicyclomine (Bentyl) and oxybutynin (Ditropan) at therapeutic concentrations primarily have a direct smooth muscle relaxant effect with little antimuscarinic action. 

Benzodiazepines also possess muscle relaxant activity. Their pharmacology is discussed in Chapter 30. Diazepam Valium) has been used for control of flexor and extensor spasms, spinal spasticity, and multiple sclerosis. The muscle relaxant effect of the benzodiazepines may be mediated by an action on the primary afferents in the spinal cord, resulting in an increased level of presynaptic inhibition of muscle tone. Polysynaptic reflexes are inhibited. The most troublesome side effect is drowsiness, which is dose dependent. Tolerance to both the therapeutic effects and the side effects develops. 

The exact mechanism of action is unclear, but it is thought that kavapyrones may act in the amygdala, producing a tranquilizing and muscle relaxant effect. 

The benzodiazepines are probably the most clinically important class of GABA-active compounds. Benzodiazepines modify affective responses to sensory perceptions specifically, they render individuals less responsive to anxiety-producing stimuli and therefore exert a strong anxiolytic action. In addition, benzodiazepines exert sedating, anticonvulsant, and muscle relaxant effects. 

Meprobamate was a further development based on another medicament (mephenesine), the muscle-relaxant effects of which had attracted attention... 

Additional studies conducted in this laboratory revealed that NO was responsible for the vascular smooth muscle relaxant effects of several different nitro-vasodilators, and that S-nitrosothiols were intermediates in the intracellular formation of NO (Ignarro et al., 1981). We showed also that NO was a potent inhibitor of human platelet aggregation, and that NO elicited such effects by... 

The fundamental neurobiological importance of the GABA A receptor is underscored by observations that even more receptor sites exist at or near this complex (Fig. 8—20). This includes receptor sites for nonbenzodiazepine sedative-hypnotics such as zolpidem and zaleplon, for the convulsant drug picrotoxin, for the anticonvulsant barbiturates, and perhaps even for alcohol. This receptor complex is hypothetically responsible in part for mediating such wide-ranging CNS activities as seizures, anticonvulsant drug effects, and the behavioral effects of alcohol, as well as the known anxiolytic, sedative-hypnotic, and muscle relaxant effects of the benzodiazepines. 

The following biological effects are mentioned in patents for 4-oxo-4M-pyrido[l,2-a]pyrimidines CNS activity, including antipyretic, tranquilizer, sedative, analgesic and/or muscle relaxant effects,55,56,59,66,72,74,... 

On the other hand, these compounds have a general depressant effect on the CNS that is, they cause a global decrease in CNS excitability that results in generalized sedation. It therefore seems possible that some of their muscle relaxant effects are caused by their sedative powers rather than a selective effect on specific neuronal reflex pathways.11,92 This observation is not to say that they are ineffective, because clinical research has shown that these drugs can be superior to a placebo in producing subjective muscle relaxation.8 20 80 97 However, the specific ability of these drugs to relax skeletal muscle remains doubtful, and it is generally believed that their muscle relaxant properties are secondary to a nonspecific CNS sedation. 

Magnesium sulfate Skeletal muscle spasms myositis Muscle relaxant effect may be caused by decreased excitability of the skeletal muscle membrane and decreased transmission at the neuromuscular junction 2°/o aqueous solution or ointment from positive pole 2°/o ointment... 

The benzodiazepine derivatives class of antianxiety agents shares the property of binding to a benzodiazepine receptor, part of the GABA receptor-chloride channel complex whose function it modulates allosterically. Not only the anxiolytic effects of the benzodiazepines, but also the anticonvulsant, sedative, or muscle relaxant effects seem to be mediated by the GABA-related mechanism. Besides the direct involvement of the GABA system, in parallel or more downstream to this, several other neurotransmitters such as serotonin have been suggested to participate in different aspects of benzodiazepine action. 

Phaeanthine Muscle relaxant effect assayed by screen grip test on rats and mice 219... 

Tricyclic antidepressants can potentiate the muscle relaxant effects of baclofen, resulting in severe hypotonic weakness (165) the combination has also been incriminated in the causation of short-term memory impairment (SEDA-11,127) (166). 

In a double-blind, placebo-controlled study in eight healthy men, zolpidem 10 mg produced statistically significant postural sway in the tandem stance test, and triazolam 0.25 mg was statistically significant only as defined by the polygonal area of foot pressure center (23). Zolpidem, which has a minimal muscle-relaxant effect, produced more imbalance than triazolam, which is known for its muscle relaxant effect. The authors suggested that in the use of hypnotics, sway derives from suppression of the central nervous system relevant to awakening rather than from muscle relaxation. 

Chlormezanone is a tranquillizer with central muscle relaxant effects. In reaction to some case reports of serious, sometimes fatal, cutaneous toxicity and after intervention by drug regulatory authorities in some European countries, all major manufacturers have stopped production of chlormezanone. It may still be available in combination products in some Asian countries. 

Chlorzoxazone is a centrally acting benzoxazole derivative with a weak muscle relaxing effect (1). It is usually used in combination with paracetamol for the treatment of painful muscle spasms. The usual dose is 500 mg tds. Drowsiness, weakness, dizziness, and gastrointestinal complaints are the most frequent unwanted effects. 

Inhibitory NANC responses are mediated by both VIP and NO.. NO. partially mediates the airway smooth muscle relaxant effects of VIP in the isolated perfused guinea-pig lung, as NOS inhibitors prevent relaxation induced by VIP but not that induced by isoproterenol (Lilly et al., 1993b). A significant and appropriately timed increase in the NO. content of lung perfusion fluid can be measured in response to VIP (Fig. 7.4). These data support the conclusion that interactions of VIP with NO. products mediate a substantial component of iNANC transmission. In human airways, NOS stimulated as a result of iNANC neurotransmission accounts for a substantial proportion of this relaxant response. Bel-visi and co-workers have shown that the a-chymotrypsin-resistant component of the human iNANC response can be abolished by treatment with NOS inhibitors (Belvisi et al., 1992). 

Bibenzyl and phenanthrenes have been found to possess smooth muscle relaxant effects [184,520,521,522],... 

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