Disease relevance of Dilevalol

• Dilevalol in severe hypertension. A multicenter trial of bolus intravenous dosing [1].
• Dilevalol reduced GFR [baseline inulin clearance: 73.3 +/- 38 ml/min/1.73 m2; after dilevalol: 63.3 +/- 28 ml/min/1.73 m2 (P less than 0.05)] and the decrease of proteinuria correlated positively with the reduction of GFR [2].
• The administration of methylscopolamine, 0.01 mg/kg both i.v. and i.m., to postinfarction animals pretreated with dilevalol, 3.0 mg/kg i.v. q 8 hr for 24 hr, reduced significantly mortality in response to subsequent posterolateral ischemia (mortality: 4 of 10 [40%] dilevalol plus methylscopolamine vs. 14 of 14 [100%] vehicle, P less than .05) [3].
• The antiarrhythmic and antifibrillatory actions of dilevalol, the R,R-isomer of labetalol, were evaluated in conscious dogs 4 to 6 days after anterior myocardial infarction [3].
• Coronary occlusion and saline or dilevalol did not modify the myocardial beta receptor density regional distribution [4].

Psychiatry related information on Dilevalol

• Impact of dilevalol on haemodynamic changes during emotional stress [5].

High impact information on Dilevalol

• Sixty-four patients were transferred to oral dilevalol treatment in combination with a diuretic, and blood pressure in this group averaged 160/100 mm Hg after 1 month of therapy [1].
• Pharmacokinetics and pharmacodynamics of dilevalol [6].
• Dilevalol, an agent that combines nonselective beta-blocking and beta 2-mediated vasodilating properties, was compared with placebo in 16 subjects with moderate hypertension in a double-blind crossover study [7].
• However, the augmentation index (averaged during the treatment period) was significantly lower with dilevalol (19%) than with atenolol (28%, p less than 0.01), corresponding to a greater decrease of 5-8 mm Hg in carotid systolic pressure compared with the brachial artery [8].
• Plasma renin activity and plasma epinephrine, aldosterone, and cyclic guanosine monophosphate levels were unchanged by dilevalol [7].

Chemical compound and disease context of Dilevalol

• Several other agents now under evaluation include bucindolol and medroxolol, and carvedilol and dilevalol (1 of the isomers of labetalol), which have been the most widely studied in hypertension [9].
• Treatment with dilevalol resulted in significantly less fatigue (p less than 0.05), bradycardia (less than 50 beats/minute) and mental depression than with propranolol, but significantly (p less than 0.05) more diarrhea/loose stools.(ABSTRACT TRUNCATED AT 250 WORDS)[10]
• Dilevalol (100 mg) or atenolol (50 mg) was given orally in 13 subjects with essential hypertension [11].
• Sixty-one patients (41 men, 20 women) aged 29-73 years, with moderate to severe hypertension, were enrolled in a multicentre study to compare the efficacy, safety, and tolerability of dilevalol (D) and captopril (C) [12].
• The effect of a single dose of 200 mg dilevalol, beta-adrenoceptor blocker with additional vasodilating properties, and 200 mg oxprenolol on haemodynamic changes induced by emotional stress have been compared in 12 male young Caucasian patients with newly diagnosed labile hypertension [5].

Biological context of Dilevalol

• Reduction in blood pressure during dilevalol administration is associated with peripheral vasodilatation, and heart rate remains essentially unchanged [13].
• At an average daily dose of dilevalol, 444 mg, heart rate at rest decreased significantly (p less than 0.01) during treatment and increased during post-treatment placebo [14].
• After both acute and subchronic treatment (mean daily dose 1,042 mg), dilevalol significantly reduced mean arterial pressure (MAP, p less than 0.0001), by significantly reducing systemic vascular resistance index (SVRI, p less than 0.001), and by not significantly altering cardiac index (CI) [15].
• However, a significant reduction versus placebo values was observed for cardiac output at 25% VO2 max, from 13.7 +/- 5.9 during placebo, to 9.4 +/- 2.5 during propranolol, and to 9.6 +/- 2.3 during dilevalol (both p less than 0.01 vs placebo) [16].
• A significant correlation was observed between the ICG R15 and the area under the plasma concentration-time curve (AUC) of dilevalol, while there was no significant correlation between the CLCR and any pharmacokinetic parameter of the agent [11].

Anatomical context of Dilevalol

• Secretion of dilevalol in breast milk [17].
• Dilevalol is 300- to 1,000-fold more potent at beta- than at alpha 1-adrenergic receptors, including those on human myocardium and mammary arteries [18].
• Prospective double-blinded clinical trials in comparison with placebo, propranolol, metoprolol and atenolol were conducted and demonstrate dilevalol to be an effective antihypertensive agent with a favorable side effect profile with a particularly low incidence of central nervous system side effects [19].
• Regional differences in the beta receptor densities were found for the atria and ventricles and for the areas within the left ventricle in cats with no coronary occlusion and dilevalol or saline [4].
• Changes in lymphocyte beta-adrenoceptor density after dilevalol oral treatment [20].

Associations of Dilevalol with other chemical compounds

• The pharmacokinetics and pharmacodynamics of dilevalol, the R,R stereoisomer of labetalol, were evaluated in nine subjects [6].
• Celiprolol and dilevalol, with beta 2-selective ISA, reduced cardiac index slightly and insignificantly, and decreased TPRI [21].
• Recent metabolic studies found beneficial effects of the newer vasodilating beta-blockers, such as dilevalol, carvedilol and celiprolol, on insulin sensitivity and the atherogenic risk factors [22].
• After a 4-week placebo washout, dilevalol was titrated from 200 to 1,600 mg once daily and metoprolol from 100 to 400 mg to a goal supine diastolic blood pressure less than 90 and greater than or equal to 10 mm Hg decrease from baseline [23].
• 3. Dilevalol decreased resting heart rate compared with nifedipine (73 vs 92 beats min-1 respectively, P < 0.01) [24].

Gene context of Dilevalol

• Dilevalol 800 mg demonstrated significant partial beta 2-adrenoceptor agonist activity by increasing finger tremor [25].
• 9. In conclusion, dilevalol 200, 400 and 800 mg demonstrated beta 1-adrenoceptor antagonist activity with no evidence of alpha 1-adrenoceptor antagonist activity [25].
• Renal function effects of dilevalol, a nonselective beta-adrenergic blocking drug with beta-2 agonist activity [26].
• Labetalol itself is an alpha 1-antagonist but dilevalol, which has negligible affinity for alpha-receptors, exerts its vasodilator effect via beta 2-agonism [27].
• The dose ratios for PS20 (means +/- s.d.) were: dilevalol 200 mg 1.1 +/- 0.1, labetalol 400 mg 2.2 +/- 0 [25].

Analytical, diagnostic and therapeutic context of Dilevalol

• Cardiac beta-blockade was assessed by use of standardized treadmill tests for 48 hours after oral dilevalol [6].
• Following oral administration, dilevalol is completely absorbed [13].
• This simplified method is readily adaptable to urine and represents the first reported HPLC assay for the quantitative determination of dilevalol in this biofluid [28].
• Lipoprotein levels before and after treatment were measured in 99 patients treated for 53.5 weeks with dilevalol (mean dose 438 mg) [23].
• Dilevalol HCl was administered as a 200-mg oral tablet and a 50-mg intravenous infusion using a randomized cross-over design [29].

References