Allylmercaptocaptopril: a new antihypertensive drug

Allylmercaptocaptopril (CPSSA) was synthesized by reacting captopril with pure allicin. Fructose-induced hypertensive groups of rats were fed a fructose-rich diet for 3 weeks, and then received the diet plus either CPSSA (40 to 56 mg or 138 to 194 micromol/L/kg/d) or captopril (80 mg or 369 micromol/L/kg/d) for 2 more weeks. CPSSA (both doses) significantly lowered blood pressure (BP) from 153.4 to 120.8 mm Hg (P <.005). Captopril gave similar results, lowering BP from 150.7 to 123 mm Hg (P <.005). CPSSA also decreased the high levels of triglycerides to normal. The new stable compound allylmercaptocaptopril combines the beneficial properties of captopril and allicin and is a potential candidate for antihypertensive drug therapy.     

Clinical evaluation of benzbromarone: a new uricosuric drug.

The long-term efficacy and safety of benzbromarone were studied in 21 nontophaceous hyperuricemic men. Daily doses of 40 or 80 mg of micronized benzbromarone caused a rapid fall in plasma urate which was maintained throughout a study period that lasted up to 1 year. A concomitant marked increase in the clearance of urate indicated that benzbromarone is a potent uricosuric drug. Initial treatment was accompanied by transient hyperuricosuria, following which urinary uric acid reverted toward, but failed to reach completely, pretreatment values. Benzbromarone did not inhibit xanthine oxidase nor did it influence the activity of purine phosphoribosyl transferases. These observations suggest that benzbromarone has no direct effect upon purine metabolic pathways, but exerts its hypouricemic action solely by blocking tubular reabsorption of uric acid. Concomitant administration of aspirin interfered only slightly with the uricosuric properties of benzbromarone. No side effects directly attributable to the drug were observed.     

Clinical evaluation of benzbromarone. A new uricosuric drug

The long-term efficacy and safety of benzbromarone were studied in 21 nontophaceous hyperuricemic men. Daily doses of 40 or 80 mg of micronized benzbromarone caused a rapid fall in plasma urate which was maintained throughout a study period that lasted up to 1 year. A concomitant marked increase in the clearance of urate indicated that benzbromarone is a potent uricosuric drug. Initial treatment was accompanied by transient hyperuricosuria, following which urinary uric acid reverted toward, but failed to reach completely, pretreatment values. Benzbromarone did not inhibit xanthine oxidase nor did it influence the activity of purine phosphoribosyl transferases. These observations suggest that benzbromarone has no direct effect upon purine metabolic pathways, but exerts its hypouricemic action solely by blocking tubular reabsorption of uric acid. Concomitant administration of aspirin interfered only slightly with the uricosuric properties of benzbromarone. No side effects directly attributable to the drug were observed.     

Direct renin inhibitors: a new approach to antihypertensive drug treatment

Hypertension remains a leading cause of morbidity and mortality, affecting more than 60 million persons in the United States. Although the past 5 decades have witnessed advances in the therapeutic modalities available to treat hypertension and a dramatic decrease in morbidity and mortality related to hypertension, adequate blood pressure control has still not been achieved in a large number of patients. Therapeutic options to manage hypertension include agents that block the sympathetic nervous system, vasodilators, agents to control plasma volume, and drugs that act at various points in the renin-angiotensin system (RAS). Inadequate control of hypertension may be due in part to incomplete blockade of the RAS pathway in some patients; targeting a point earlier in this cascade might possibly improve control. Direct renin inhibitors, a new class of antihypertensive drugs, block the RAS pathway at the point of activation. Inhibition of renin prevents the downstream production of the potent vasoconstrictor angiotensin II, which is responsible for increasing blood pressure. Recent clinical data with aliskiren, a new direct renin inhibitor, suggest favorable results in patients with hypertension and a possible new treatment option.     

Clinico-experimental study of the new antihypertensive preparation abletol (labetalol)

Albetol treatment was administered to 31 patients with stable hypertension. The drug produced a drop in the heart rate, cardiac index and a slight decrease of total peripheral resistance, due to albetol simultaneous alpha- and beta-blocking action. There were no marked orthostatic changes. Blood pressure, cardiac index and heart rate values increased to a smaller extent in response to exercise. Experimental studies in the frog atrium showed different effects of Albetol and Propranolol on transmembrane ion currents. Albetol did not affect renal function at rest, nor the pattern of its change under physical stress and in an orthostatic position. It is suggested that albetol alpha-blocking action is predominant in the orthostatic test, while beta-blocking effect prevails during exercise.