diclofurime and Hypertension

1. Trans-diclofurime has been shown to be a potent group II calcium antagonist in in vitro and in vivo test systems. In contrast to the dihydropyridines, group II calcium antagonists have a reduced propensity to cause reflex tachycardia due to well-balanced inhibitory effects in smooth muscle and heart. Since effects on autonomic reflexes are more reliably assessed in conscious animals, the cardiovascular effects of trans-diclofurime have been examined and compared to those of nifedipine, verapamil and diltiazem in the conscious spontaneously hypertensive rat (SHR). 2. Each SHR had an indwelling catheter in the femoral artery to record mean arterial pressure (MAP) and heart rate (HR) and a cannula in the femoral vein for drug infusion over 1 min. 3. Nifedipine (0.1-3.0 mumol kg-1 i.v.) caused dose-related falls in MAP accompanied by dose-related increases in HR. Trans-diclofurime and verapamil (0.3-3.0 mumol kg-1 i.v.) also caused dose-related decreases in MAP, but significant tachycardia was only seen at 1.0 and 3.0 mumol kg-1. Trans-diclofurime (0.3 mumol kg-1) induced a significant fall in HR. Diltiazem (1.0-10.0 mumol kg-1 i.v.) induced dose-related falls in MAP, significant bradycardia was evident with 1.0 mumol kg-1 and tachycardia with 10 mumol kg-1. Trans-diclofurime and diltiazem induced less tachycardia than nifedipine and verapamil for equivalent falls in MAP. 4. These results suggest that trans-diclofurime is a potent antihypertensive agent in conscious SHR and, like diltiazem, the hypotensive effects are associated with less tachycardia than is usually apparent with calcium antagonists such as nifedipine or verapamil. S. The cardiovascular effects of trans-diclofurime in conscious SHR are those expected of a class II calcium antagonist and are consistent with its proposed mode of interaction with the diltiazem site in the calcium channel.

Topics: Animals; Blood Pressure; Calcium Channel Blockers; Diltiazem; Heart Rate; Hemodynamics; Hypertension; Male; Nifedipine; Oximes; Rats; Rats, Inbred SHR; Time Factors; Verapamil

Diclofurine is a new ketone-oxime derivative with potent peripheral vasodilating properties. Its hypotensive effects were studied in 24 patients suffering from severe hypertension resistant to combinations of most hypotensive drugs. In 22 patients who received diclofurime alone the blood pressure decreased from mean values of 194 +/- 1/118 +/- 3 to 166 +/- 4/97 +/- 3 mmHg after the weeks of treatment and remined at simular levels on further examinations. Most remarkably, the fall in BP was accompanied by a decrease of 15 beats/minute in supine heart rate. The mean daily dosage of diclofurime was 518 mg, the drug being taken in three divided doses. In 7 cases where diclofurime was combined with acebutolol either from the start or (in 5 cases) after an initial period of monotherapy, the efficacy of the treatment was enhanced by the beta-blocking agent. Out of 24 patients studied only one failed to respond. The new drug was generally well tolerated. Diclofurime appears to be one of the most active and best tolerated drugs for long-term oral treatment of arterial hypertension.

Topics: Acebutolol; Adult; Aged; Antihypertensive Agents; Drug Therapy, Combination; Female; Furans; Humans; Hypertension; Male; Middle Aged; Oximes; Vasodilator Agents