Effect of the novel T-selective calcium channel antagonist mibefradil on kidney function in comparison with amlodipine.
In the present study, the renal effects of mibefradil (CAS 116666-63-8), a novel calcium channel antagonist which more selectively blocks T-type than L-type calcium channels, was tested by applying clearance techniques to anaesthetized rats. The effects of mibefradil on kidney function and on arterial blood pressure were compared with those of the long acting dihydropyridine-type calcium antagonist amlodipine (CAS 88150-42-9). The results show that, within a dosage range of 0.1 to 1.0 mg/kg i.v., mibefradil induced a dose-dependent decrease of arterial blood pressure. Kidney function was not significantly affected at a dose of 0.1 mg/kg. By increasing the dose to 0.3 mg/kg, mibefradil induced a significant increase in urine flow, renal sodium, chloride and potassium excretion. Also fractional sodium and chloride excretions were significantly enhanced at this dose. The diuretic and saluretic effects of mibefradil were accompanied by a significant increase in the glomerular filtration rate. At the highest dose of 1 mg/kg used, the blood pressure lowering effect of mibefradil was most pronounced and glomerular filtration rate rose only slightly and not significantly. At this dose, the enhancement of urine flow and urinary electrolyte excretion was smaller than at the dose of 0.3 mg/kg. The actions of mibefradil were qualitatively similar to those of the dihydropyridine derivate amlodipine which at a dose of 0.3 mg/kg produced nearly identical renal effects to mibefradil, but exerted stronger antihypertensive effects. This study demonstrates that mibefradil shares with amlidopine the property to induce, at appropriate doses, diuretic and saluretic effects with a concomitant increase in glomerular filtration rate.
Greven
J
J
Department of Pharmacology and Toxicology, Rheinisch-Westfälische Technische Hochschule Aachen, Germany.
D017311:Amlodipine / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D007677:Kidney Function Tests; D008297:Male; D020748:Mibefradil; D011188:Potassium / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014563:Urodynamics / Q000187:drug effects
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D013764:Tetrahydronaphthalenes; D017311:Amlodipine; D020748:Mibefradil; D012964:Sodium; D011188:Potassium