Disease relevance of mephenesin

• Abnormal smooth-muscle contractility may be a major cause of disease states such as hypertension, and a smooth-muscle relaxant that modulates this process would be useful therapeutically [1].
• The effectiveness of cyclobenzaprine hydrochloride, a new tricyclic skeletal muscle relaxant, was shown in patients with long-term intractable pain of cervical and lumbar origin aggravated by skeletal muscle spasm and tenderness [2].
• Loss of endothelium-dependent relaxant activity in the pulmonary circulation of rats exposed to chronic hypoxia [3].
• However, only pharmacotherapy for urge incontinence has advanced to the level at which several drugs that have undergone rigorous scientific testing using randomized controlled trials have received FDA approval; these are the antimuscarinic and anticholinergic/direct smooth muscle relaxant drugs [4].
• Here we show that inhibition of G(i) proteins with pertussis toxin (PTX) permits a full phospholamban phosphorylation and a de novo relaxant effect following beta(2)-AR stimulation, converting the localized beta(2)-AR signaling to a global signaling mode similar to that of beta(1)-AR [5].

Psychiatry related information on mephenesin

• Bladder regimen, including early toilet training from the age of 1.5 years and detrusor relaxant drugs for the treatment of incontinence from ages 4 to 6 years, was introduced to all patients [6].
• Tolerance to the abecarnil-induced muscle relaxant effects and decreased locomotor activity developed within 21 days [7].
• IMPLICATIONS: The dose of muscle relaxant (succinylcholine) recommended in modified electroconvulsive therapy is not based on empirical research [8].
• These results may suggest that, in diabetes, the relaxant effects of the Rho-kinase inhibitors may not be changed and thus, they may have a beneficial therapeutic effect in diabetic erectile dysfunction [9].
• Moreover, it produced no acute muscle relaxant effect and did not induce drug dependence and withdrawal reactions after chronic administration in mice [10].

High impact information on mephenesin

• Since GlyRs are involved in motor reflex circuits of the spinal cord and provide inhibitory synapses onto pain sensory neurons, these agents may provide lead compounds for the development of muscle relaxant and peripheral analgesic drugs [11].
• Administration of a vascular smooth muscle relaxant prevented onset of myocardial necrosis [12].
• We then studied the smooth-muscle relaxant responses to stimulation by an electrical field and to nitric oxide [13].
• The muscle relaxant vecuronium is sometimes administered to facilitate mechanical ventilation [14].
• We report here identification in porcine brain of a novel peptide of 26 amino-acid residues, eliciting a pharmacological spectrum very similar to that of ANP, such as natriuretic-diuretic, hypotensive and chick rectum relaxant activities [15].

Chemical compound and disease context of mephenesin

• The results show that superoxide and other radicals generated after acute hypertension interfere with acetylcholine-induced endothelium-dependent vasodilation, probably because they destroy the endothelium-derived relaxant factor [16].
• In arteries without endothelium, DOCA-salt hypertension caused a threefold increase in contractile sensitivity for arginine vasopressin, norepinephrine, and KCl; a 50% reduction in maximal relaxation to isoproterenol; and a threefold decrease in relaxant sensitivity to sodium nitroprusside [17].
• The relaxant action of isoproterenol on 1.0 mM barium contractures of rat arteries was inhibited by treatment with ouabain or with potassium-free solution [18].
• 1. Adenosine is a regulator of mesenteric vasodilation involved in auto-regulation and post-prandial hyperemia, but the adenosine receptor subtype involved in this relaxant effect is poorly characterized [19].
• In contrast, glibenclamide inhibited the relaxant effects of the three drugs during hypoxia + hypercapnia [20].

Biological context of mephenesin

• The atrial substance that copurified with the smooth muscle relaxant activity in both peaks caused natriuresis when injected into conscious rats [21].
• Nine additional postoperative patients were studied with ACH followed by inhalation of 80 ppm nitric oxide, an endothelium-independent smooth muscle relaxant [22].
• Nitric oxide (NO) has been identified as endothelium-derived relaxing factor (EDRF), which, in addition to its relaxant effects on vascular smooth muscle cells, is also a potent inhibitor of platelet aggregation [23].
• The relaxant effects of adenosine, 3-isobutyl-1-methylxanthine, forskolin, sodium nitroprusside, and 8-bromo-cGMP were tested under conditions where myosin phosphorylation was at basal levels (0.08 +/- 0.02 mol Pi/mol light chain) [24].
• Papaverine (0.27 mM) (a smooth-muscle relaxant) abolished the pulmonary microvascular response to substance P in Ringer's-perfused lungs, and meclofenamate (0.15 mM) (a cyclooxygenase inhibitor) attenuated the pulmonary vasoconstriction and lung weight increase [25].

Anatomical context of mephenesin

• Increases in cyclic GMP levels may not mediate relaxant effects of sodium nitroprusside, verapamil and hydralazine in rat vas deferens [26].
• Vasoactive intestinal peptide, a smooth-muscle relaxant neuropeptide with neurotransmitter properties, was relaxed during electrical field stimulation of guinea pig trachea [27].
• The muscle relaxant dantrolene sodium acts directly and specifically on skeletal muscle, unlike other pharmacological agents which affect the central nervous system or act at the nueromuscular junction [28].
• Histamine H2 receptor agonists caused only small relaxant responses in about 30% of strips from gallbladder body, but were without effect in gallbladder neck and cystic duct [29].
• CONCLUSIONS: Active tone is present in the smooth muscle esophagus and can be modulated by a smooth muscle relaxant [30].

Associations of mephenesin with other chemical compounds

• In airway smooth muscle its relaxant action is accompanied by hyperpolarization of the membrane and elevation of the level of intracellular cyclic AMP [31].
• The smooth muscle relaxant papaverine did not attenuate the response; therefore, such reductions in diameter probably reflect a structural modification of the arterial wall rather than sustained contraction of smooth muscle [32].
• A characteristic feature of airway smooth muscle is its relative sensitivity to relaxant effects of beta adrenergic agonists when contracted by inflammatory mediators, such as histamine, vs. resistance to these relaxant effects when contracted by muscarinic agonists [33].
• These data indicate that inflamed lungs are more sensitive to the contractile effects of SP because it is less efficiently degraded by NEP and are less sensitive to the relaxant effects of VIP because it is more efficiently degraded by a tryptic enzyme [34].
• A possible explanation for the altered diastolic pressure-volume relationships with nitroprusside might be a direct relaxant effect of nitroprusside on ventricular muscle, similar to its known relaxant effect on vascular smooth muscle [35].

Gene context of mephenesin

• Bovine PTH-(3-34) an established in vitro antagonist of PTH, partially inhibited the relaxant effect of PTHrP [36].
• The influence of NOS inhibitors on the relaxant effect of VIP was determined in isolated smooth muscle cells and smooth muscle strips of wild-type and knockout mice [37].
• In contrast, neither [beta Ala8]-NKA (4-10) nor [MePhe7]-NKB (both at a concentration of 1 microM), selective synthetic agonists for NK2 and NK3 receptors, exerted significant relaxant effects [38].
• Because NF-kappaB induces cyclooxygenase-2 (COX-2) to increase synthesis of prostaglandins (PGs), including the potent airway anti-inflammatory and smooth muscle relaxant PGE(2), we investigated whether LPS causes short-term PGE(2)-dependent relaxation of mouse isolated trachea [39].
• The precocious expression of CYP2C in SIDS could result in a higher production of epoxyeicosatrienoic acids in the neonate, believed to act as relaxant of pulmonary smooth muscles [40].

Analytical, diagnostic and therapeutic context of mephenesin

• The longitudinal smooth muscle layer of the guinea pig ileum, where neurotensin has both a direct relaxant and an indirect contractile action, has been used extensively as a biological assay system for neurotensin [41].
• No significant difference was observed among the CABGs with different duration of transplantation, whereas the relaxant responses of different segments along the entire length of a CABG were markedly different [42].
• Exposure to NOLA at 10 mumol/l reduced stimulation-induced relaxations; this reduction was significantly greater in tissues from the diabetic group than from the control group (p < 0.05), probably as a consequence of the smaller relaxant responses in muscles from diabetic rats [43].
• Proximal left circumflex vessels exposed to ischaemia and reperfusion showed enhanced sensitivity to the relaxant effects of SIN-1 compared to control proximal vessels obtained from the same hearts [44].
• A series of 2-[( alkoxycarbonyl )amino]-4(5)-phenyl-2-imidazolines was prepared and evaluated for central nervous system (CNS) effects (antidepressant, anticonvulsant, muscle relaxant, and depressant) in animal models [45].

References