Muscle relaxation, mechanism

The precise mechanism of nitrate action is not cleady understood and may be a combination of many factors. The basic pharmacologic action of nitrates is a relaxation of most vascular smooth muscle, eg, vascular, bronchial, gastrointestinal, uretal, uterine, etc. Vascular smooth muscle relaxation is a... 

In the presence of calcium, the primary contractile protein, myosin, is phosphorylated by the myosin light-chain kinase initiating the subsequent actin-activation of the myosin adenosine triphosphate activity and resulting in muscle contraction. Removal of calcium inactivates the kinase and allows the myosin light chain to dephosphorylate myosin which results in muscle relaxation. Therefore the general biochemical mechanism for the muscle contractile process is dependent on the avaUabUity of a sufficient intraceUular calcium concentration. 

Anxiolytics are drugs used for the treatment of anxiety disorders. Apart from benzodiazpines, a frequently used anxiolytic is the 5HT1A (serotonin) receptor agonist buspiron, which has no sedative, amnestic or muscle-relaxant side effects, but whose action takes about a week to develop. Furthermore, it is less efficaceous than the benzodiazepines. Buspiron s mechanism of action is not fully understood. 

Quinazolines containing an electron-rich carbocyclic ring have been associated with smooth muscle relaxant activity. The mechanism of action (phosphodiesterase inhibition, a- adrenergic blockade) and organ selectivity (bronchi, vascular smooth muscle) vary greatly with substitution on the heterocyclic ring. 

Changes in heart rate also affect the contractility of the heart. As heart rate increases, so does ventricular contractility. The mechanism of this effect involves the gradual increase of intracellular calcium. When the electrical impulse stimulates the myocardial cell, permeability to calcium is increased and calcium enters the cell, allowing it to contract. Between beats, the calcium is removed from the intracellular fluid and the muscle relaxes. When heart rate is increased, periods of calcium influx occur more frequently and time for calcium removal is reduced. The net effect is an increase in intracellular calcium, an increased number of crossbridges cycling, and an increase in tension development. 

The skeletal muscle relaxant that acts directly on the contractile mechanism of the muscle fibers is... 

Bisbenzylisoquinoline alkaloids are dimeric benzyltetrahydroisoquinoline alkaloids that are known for their pharmacological activities. A well-described example is the muscle relaxant (+)-tubocurarine, which in crude form serves as an arrow poison for South American Indian tribes. In the biosynthesis of this broad class of dimeric alkaloids, it has been postulated that the mechanism of phenol coupling proceeds by generation of phenolate radicals followed by radical pairing to form either an inter- or intramolecular C - O or C - C bond. Enzyme studies on the formation of bisbenzylisoquinoline alkaloids indicated that a cytochrome P-450-dependent oxidase catalyzes C - O bound formation in the biosynthesis of berbamunine in Berberis cell suspension culture.15 This enzyme, berbamunine synthase (CYP80A1), is one of the few cytochromes P-450 that can be purified to... 

Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside, and nitric oxide evidence for the involvement of S-nitrosothiols as active intermediates. /. Pharmacol. Exp. Then 218 (1981), p. 739-749... 

ATP is used not only to power muscle contraction, but also to re-establish the resting state of the cell. At the end of the contraction cycle, calcium must be transported back into the sarcoplasmic reticulum, a process which is ATP driven by an active pump mechanism. Additionally, an active sodium-potassium ATPase pump is required to reset the membrane potential by extruding sodium from the sarcoplasm after each wave of depolarization. When cytoplasmic Ca2- falls, tropomyosin takes up its original position on the actin and prevents myosin binding and the muscle relaxes. Once back in the sarcoplasmic reticulum, calcium binds with a protein called calsequestrin, where it remains until the muscle is again stimulated by a neural impulse leading to calcium release into the cytosol and the cycle repeats. 

Despite the many decades amyl nitrite and glyceryl trinitrate have been used in therapy, it is only in recent years that the molecular mechanism of action of the nitrovasodilators has begun to be understood [3-5]. The drugs act by releasing nitric oxide (NO, a neutral radical usually written simply as NO), which produces smooth muscle relaxation in blood vessels and exhibits a range of other biological effects [6]. Thus, bioactivation to yield NO precedes the main therapeutic effect of nitrovasodilators and would justify their classifica-... 

Waldman, S. A., and Murad, F., 1988, Biochemical mechanisms underlying vascular smooth muscle relaxation the guanylate cyclase-cychc GMP system, J. Cardiovasc. Phamacol. 12 8115-118. 

Buspirone is an extremely specific drug that could possibly represent a new chemical class of anxiolytics—azaspirones. As an anxiolytic, its activity is equal to that of benzodiazepines however, it is devoid of anticonvulsant and muscle relaxant properties, which are characteristic of benzodiazepines. It does not cause dependence or addiction. The mechanism of its action is not conclusively known. It does not act on the GABA receptors, which occurs in benzodiazepine use however, it has a high affinity for seratonin (5-HT) receptors and a moderate affinity for dopamine (D2) receptors. Buspirone is effective as an anxiolytic. A few side effects of buspirone include dizziness, drowsiness, headaches, nervousness, fatigue, and weakness. This drug is intended for treatment of conditions of anxiety in which stress, muscle pain, rapid heart rate, dizziness, fear, etc. are observed in other words, conditions of anxiety not associated with somewhat common, usual, and everyday stress. Synonyms for buspirone are anizal, axoren, buspar, buspimen, buspinol, narol, travin, and others. 

Dantrolene is a drug that causes spastic muscle contraction. Unlike other muscle relaxants, it has a direct effect on the contractile mechanism by interfering in the process of calcium ion release from the sarcoplasmic reticulum. This results in a lack of coordination in the mechanism of excitation—contraction of skeletal muscle, which has a greater effect on fast muscle fibers than on slow muscle fibers. Dantrolene is used for controlling the onset of clinical spasticity resulting from serious clinical cases such as wounds, paralysis, cerebral palsy, and disseminated sclerosis. Synonyms of this drug are dantrium and danlen. 

Pharmacology These agents are synthetic adrenocortical steroids with basic glucocorticoid actions and effects. Glucocorticoids may decrease number and activity of inflammatory cells, enhance effect of beta-adrenergic drugs on cyclic AMP production, inhibit bronchoconstrictor mechanisms, or produce direct smooth muscle relaxation. Inhaler use provides effective local steroid activity with minimal systemic 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. 

Magnesium sulfate, applied intravenously is often used as tocolytic. The mechanism of action is not completely clear but might involve a competition with calcium on the cellular level. Precautions in the sense of magnesium plasma level monitoring must be taken in patients with renal insufficiency since this divalent kation is eliminated by the kidneys. Relatively high plasma concentrations are necessary to achieve a sufficient tocolysis. The relatively frequent side effects are respiratory depression, depressed reflexes, headaches, palpitation and skin flushing in the mother and muscle relaxation and, rarely, CNS depression in the fetus. 

Agents affecting the central nervous system and have muscle relaxant activity together with a unique mechanism of action, i.e. dantrolene, will be briefly discussed here. 

Proposed mechanism by which nitroglycerin and the organic nitrates produce relaxation in vascular smooth muscle. Nitrates induce endothelial cells to release NO or a nitrosothiol (endothelium-derived releasing factor, or EDRF). EDRF activates the enzyme guanylate cyclase, which causes the generation of cyclic guanosine monophosphate (GMP), producing a decrease in cytosolic free calcium. The end result is vascular smooth muscle relaxation. SH, sulfhydryl. 

Smooth muscle relaxation, central nervous system (CNS) excitation, and cardiac stimulation are the principal pharmacological effects observed in patients treated with theophylline. The action of theophylline on the respiratory system is easily seen in the asthmatic by the resolution of obstruction and improvement in pulmonary function. Other mechanisms that may contribute to the action of theophylline in asthma include antagonism of adenosine, inhibition of mediator release, increased sympathetic activity, alteration in immune cell function, and reduction in respiratory muscle fatigue. Theophylline also may exert an antiinflammatory effect through its ability to modulate inflammatory mediator release and immune cell function. 

Inhibition of cyclic nucleotide phosphodiesterases is widely accepted as the predominant mechanism by which theophylline produces bronchodilation. Phosphodiesterases are enzymes that inactivate cAMP and cyclic guanosine monophosphate (GMP), second messengers that mediate bronchial smooth muscle relaxation. 

Sildenafil is a selective inhibitor of cGMP-specific PD-5 and therefore inhibits the degradation of cGMP PD-5, the predominant type in the corpus cavernosum, also is present in other tissues (e.g., lungs, platelets, and eye). TTie selective inhibition of this enzyme facilitates the release of nitric oxide and smooth muscle relaxation of the corpus cavernosa. Sildenafil enhances erection by augmenting nitric oxide-mediated relaxation pathways. It has been suggested that sildenafil s mechanism of action is due to cross-talk between cGMP- and cAMP-dependent transduction pathways within the cavernous muscles. 

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. 

Mechanism of Action A centrally-acting skeletal muscle relaxant whose exact mechanism is unknown. Effects may be due to its CNS depressant actions. Therapeutic Effect Relieves muscle spasms and pain. 

Mechanism of Action A benzodiazepine that depresses all levels of the CNS by enhancing the action of gamma-aminobutyric acid, a major inhibitory neurotransmitter in the brain. Tircrapeutic Effect Produces anxiolytic effect, elevates the seizure threshold, produces skeletal muscle relaxation. 

Mechanism of Action Aglucose elevating agent that promotes hepatic glycogenoly-sis, gluconeogenesis. Stimulates production of cyclic adenosine monophosphate (cAMP), which results in increased plasma glucose concentration, smooth muscle relaxation, and an inotropic myocardial effect. Therapeutic Effect Increases plasma glucose level. 

Mechanism of Action A benzodiazepine that enhances the action of the inhibitory neurotransmitter gamma-aminobutyric acid in the CNS, affecting memory as well as motor, sensory, and cognitive function. Therapeutic Effect Produces anxiolytic, anticonvulsant, sedative, muscle relaxant, and antiemetic effects. 

Mechanism of Action Acarbamate derivative of guaifenesin that causes skeletal muscle relaxation by general CNS depression. Therapeutic Effect Relieves muscle spasticity. 

Mechanism of Action A benzodiazepine that potentiates the effects of gamma-aminobutyric acid and other inhibitory neurotransmitters by binding to specific receptors in the CNS. Therapeutic Effect Produces sedative effect and skeletal muscle relaxation. 

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