Disease relevance of CLENTIAZEM

• The most frequently reported treatment-related adverse events with clentiazem were asthenia, headache (both 7.9%), first-degree atrioventricular block and dizziness (both 4.4%) [1].
• Pretreatment with clentiazem lessened the decrease in cerebral blood flow (control, 4.8 +/- 1.4%; clentiazem, 14.1 +/- 4.1% of the preischemic level; P < .05) and prevented the disappearance of electroencephalographic activity in some rats during ischemia [2].
• The effect of a new calcium antagonist, TA3090 (clentiazem), on experimental transient focal cerebral ischemia in cats [3].
• Clentiazem protects against chronic cerebral vasospasm in rabbit basilar artery [4].
• Clentiazem prevented or reduced many of the changes in the basilar artery caused by the subarachnoid hemorrhage [4].

High impact information on CLENTIAZEM

• At submaximal exercise, clentiazem (40, 80 and 120 mg/day) decreased rate-pressure product, mainly as a result of a decrease in heart rate [1].
• Clentiazem also significantly reduced the expression of AP-1 induced by rPDGF-AB (P < .05) [5].
• Effects of clentiazem on cerebral ischemia induced by carotid artery occlusion in stroke-prone spontaneously hypertensive rats [2].
• CONCLUSIONS: The vascular damage associated with chronic cerebral vasospasm is related to calcium entry into the smooth muscle and endothelial cells, and possibly sympathetic nerve terminals, through calcium channels sensitive to clentiazem, which suggests that clentiazem may be of value in the management of chronic cerebral vasospasm [4].
• Clentiazem reduces infarct size in rabbit middle cerebral artery occlusion [6].

Chemical compound and disease context of CLENTIAZEM

• Treatment with clentiazem prevented epinephrine-induced death (P < .05), and attenuated the ventricular ischemic lesions and fibrosis, in a dose-dependent manner [7].
• Normal and failing CMH hearts were either untreated (control) or perfused at the onset of global ischemia with one of the following combinations: cold cardioplegia alone (St. Thomas' Hospital cardioplegic solution, 4 degrees C, infused for 2 min), cold cardioplegia + 10 nM diltiazem, or cold cardioplegia + 10 nM clentiazem [8].
• Clentiazem (TA-3090, CAS 96125-53-0), a new benzothiazepine Ca++ antagonist, was orally administered to inpatients with essential hypertension at a dose of 30 mg at 8:00 a.m. once (n = 5) or daily for 2 weeks (n = 22) [9].

Biological context of CLENTIAZEM

• Inhibition of vascular smooth muscle cell proliferation by the calcium antagonist clentiazem: role of protein kinase C [10].
• Moreover, treatment with clentiazem leads to a marked decrease in the number of specific phorbol ester binding sites [10].
• Clentiazem (10 micrograms/kg/min) lowered arterial pressure by 16% and doubled glomerular filtration rate (GFR) in MWR [11].
• Clentiazem appear to cause inhibition of PKC translocation that is induced by phorbol esters and PDGF-BB and the phosphorylation of the 80 kDa protein substrate of PKC in vascular smooth muscle cells [10].
• Single and multiple oral dose pharmacokinetics of clentiazem in normal volunteers [12].

Anatomical context of CLENTIAZEM

• Also, neutrophil accumulation at the epicardial side of the infarct, at the edge of salvaged myocardium, and estimated by tissue myeloperoxidase measurement, was reduced by 50% in treated dogs (clentiazem: 17.2 +/- 2.8; controls: 32.3 +/- 2.7 x 10(6) neutrophils/g) [13].
• 1. We examined the mechanisms underlying Ca2+-induced relaxation in the presence of clentiazem, a new Ca2+-antagonist, in depolarized coronary arteries of the dog [14].
• The postischemic cardioprotection by calcium antagonists and the interplay between neutrophils and regional myocardial blood flow were investigated further, using clentiazem, a new potent calcium channel blocker derived from diltiazem [13].
• Azidobutyryl clentiazem, a new photoactivatable diltiazem analog, labels benzothiazepine binding sites in the alpha 1 subunit of the skeletal muscle calcium channel [15].
• 2. Ca2+ (3 x 10(-5)-3 x 10(-3) M) caused an unexpected relaxation in the presence of a high concentration of clentiazem (10(-6) M) in coronary, but not in mesenteric or renal arteries [14].

Associations of CLENTIAZEM with other chemical compounds

• When combined with cyclosporine, diltiazem and clentiazem interacted synergistically (mean survival time increased to 16.8 +/- 3.4 days for diltiazem and 15.8 +/- 1.4 days for clentiazem) [16].
• Left atrial and left ventricular papillary muscle contractile responses to isoproterenol were reduced compared to controls in groups treated with clentiazem alone, but combined with epinephrine, clentiazem restored left atrial responses and enhanced left ventricular papillary responses to isoproterenol [7].
• Therefore, clentiazem reduced mean arterial pressure through a decrease in total peripheral resistance, and released epinephrine was associated with intracellular potassium influx (urinary potassium did not change) [17].
• The binding properties of a new 1,5-benzothiazepine, clentiazem (TA-3090), were investigated in rat cerebral cortex and skeletal muscle membranes with [3H]diltiazem and [3H]nitrendipine as radioligands [18].
• Intravenous and intraduodenal administration of RS-5773, diltiazem or clentiazem produced dose-dependent suppressions of the ischemic ECG changes [19].

Gene context of CLENTIAZEM

• PDGF-induced prolifertion of these cells is markedly inhibited by clentiazem [10].
• The aortas of the clentiazem groups demonstrated significantly less ORO staining than CCT diet controls in thoracic aorta after 6 weeks and abdominal aorta after 12 weeks [20].
• To better characterize the reduced coronary sensitivity to clentiazem in the presence of heart failure, the contributions of the NO synthase and the cyclooxygenase pathways were evaluated [21].
• Diltiazem, clentiazem and their acidic and basic metabolites extractable with tert-butyl methyl ether, which are all 2,3,5-trisubstituted-1,5-benzothiazepines, were analysed by positive ion electron ionization (PIEI) mass spectrometry, and the structures of fragment ions and their fragmentation pathways were investigated [22].
• Pretreatment with the Ca channel blocker clentiazem (10(-7) mol/L) itself depressed developed pressure by 53+/-9% [23].

Analytical, diagnostic and therapeutic context of CLENTIAZEM

• After washout and a 1-week placebo run-in period, patients received 20, 40, 80 or 120 mg/day of clentiazem tablets or placebo as a twice-daily dosage for 1 week of treatment after 1 week of dose titration [1].
• However, after an initial recovery to preocclusion values at 30-min reperfusion in both groups, flow declined to 50% normal (P < .05) in control animals after 3 and 6 hr in midwall and subendocardium, but the change was remarkably attenuated (P < .05) in subendocardium of clentiazem-treated dogs [13].
• One group was given clentiazem: 100 micrograms/kg at 5 min before reperfusion followed by a perfusion of 1 microgram/kg/min until sacrifice; controls received saline [13].
• Pharmacokinetics of clentiazem after intravenous and oral administration in healthy subjects [24].
• We therefore evaluated the cardioprotective interaction of diltiazem, clentiazem, and cold cardioplegia in both normal and failing ischemic hearts [8].

References