Disease relevance of Semotiadil

• The well-known high vasoselectivity of semotiadil in combination with a relatively low Ca2+ channel antagonistic influence on the heart makes semotiadil an interesting candidate for the treatment of coronary heart diseases [1].
• Semotiadil (10 and 30 mg/kg) produced a dose-dependent hypotension that persisted for 18 hr at 30 mg/kg [2].
• The frequency-dependent suppressant effect on FRP of semotiadil is also noteworthy in the treatment of reentrant supraventricular tachycardia that involves the AV node [3].
• During sinus rhythm, semotiadil as well as verapamil and diltiazem induced comparable depressant effects on AV-nodal conduction time and, during tachycardia, a comparable enhancement of this effect [4].
• Semotiadil inhibits the development of right ventricular hypertrophy and medial thickening of pulmonary arteries in a rat model of pulmonary hypertension [5].

High impact information on Semotiadil

• To identify the binding domain of a new Ca2+ antagonist semotiadil on L-type Ca2+ channels from skeletal muscle, photolabeling was carried out by using an azidophenyl derivative of [3H]semotiadil [6].
• Efficient identification of photolabelled amino acid residues by combining immunoaffinity purification with MS: revealing the semotiadil-binding site and its relevance to binding sites for myristates in domain III of human serum albumin [7].
• Human serum albumin (HSA) was photolabelled with an azidophenyl derivative of semotiadil, FNAK [(+)-(R)-3,4-dihydro-2-[5-methoxy-2-[3-[N-methyl-N-[2-(3-azidophenoxy)-ethyl]amino]propoxyl]phenyl]-4-methyl-2H-1,4-benzothiazin-3-(4H)-one], since HSA is a major binding protein for semotiadil in serum [7].
• Effects of semotiadil fumarate, a novel Ca2+ antagonist, on cytosolic Ca2+ level and force of contraction in porcine coronary arteries [8].
• Semotiadil even at the higher concentration (10 microM) did not displace specific binding of [3H]-pyrilamine to bovine cerebellar membranes [8].

Chemical compound and disease context of Semotiadil

• Verapamil and semotiadil exhibited a significantly greater effect than diltiazem on the mean ventricular cycle length (VCLmeun), on the maximal ventricular cycle length (VCLmax) and on the standard deviation of the VCL (SD(VCL)) during atrial flutter [4].
• These results indicate that combined daily dosing of semotiadil, especially with enalapril, each at relatively low doses may be able to control hypertension in a continuous manner [9].

Biological context of Semotiadil

• To the same semotiadil derivatives, the cardiac counterpart showed distinct and different binding characteristics: semotiadil and its photoaffinity analog D51-4700 inhibited [3H]PN200-110 binding to cardiac membrane preparations with IC50 values of 13-20 microM, which are 10 times higher than those in skeletal muscle [10].
• Intrarenal arterial infusion of semotiadil resulted in a significant increase in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow, urinary excretion of electrolytes and renin release [11].
• Effects of semotiadil (SD-3211), a benzothiazine calcium antagonist, on blood pressure and atrioventricular conductivity in anesthetized dogs [3].
• Quantitative structure-activity relationships of Ca(2+)-antagonistic semotiadil congeners [12].
• Semotiadil showed a dose-dependent inhibition of platelet aggregation in vitro with all the agents examined [13].

Anatomical context of Semotiadil

• The Ca2+ channel blocking compound semotiadil showed the most pronounced rate-dependent effects on the AV node [14].
• The influence of semotiadil fumarate, a novel vasoselective Ca2+ channel antagonist with a benzothiazine skeleton, was measured on the high-threshold Ca2+ current ICa,L in guinea-pig ventricular myocytes prepared by coronary perfusion with collagenase solution [1].
• Effects of semotiadil, a novel calcium antagonist, on the retina and optic nerve head circulation [15].
• These results suggest that semotiadil and SD-3212 inhibit contractions of vascular smooth muscle (VSM) not only through blockade of voltage-dependent Ca2+ channels but also through other mechanisms, such as inhibition of Ca2+ release from Ca2+ stores or decrease in sensitivity of the contractile elements to Ca2+ [16].
• Effects of semotiadil on the voltage-dependent Ca current (ICa) were investigated in dispersed smooth muscle cells of the rabbit portal vein [17].

Associations of Semotiadil with other chemical compounds

• Atrioventricular conduction and the effective refractory period of the AV node were most affected by diltiazem and semotiadil [14].
• Effects of semotiadil, a novel Ca2+ channel antagonist, on the electrical activity of Langendorff-perfused guinea pig hearts in comparison with diltiazem, amlodipine and nifedipine [14].
• After an instantaneous injection of semotiadil, levosemotiadil, or Evans Blue (a marker of BSA), each outflow time profile from the liver was analyzed by a two-compartment dispersion model [18].
• Effects of semotiadil fumarate (SD-3211) and its enantiomer, SD-3212, on the changes in cytosolic Ca2+ and tension caused by KCl and norepinephrine in isolated rat aortas [16].

Gene context of Semotiadil

• These results indicate that semotiadil may have the strongest antioxidant activity on LDL among the calcium antagonists examined [19].

Analytical, diagnostic and therapeutic context of Semotiadil

• Changes in NB(retina) from the baseline in the semotiadil group was significantly greater than those in the control group 50 min or later after the administration (P < 0.0500, Mann-Whitney test) [15].
• Twenty-four hours later (day 1), oral administration of semotiadil (10, 30, or 100 mg/kg per day) or diltiazem (100 or 300 mg/kg per day) was initiated [5].

References