3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5- dicarboxylate Effect on Induced Contractions by Hydrogen Peroxide on Trachea Smooth Muscle

* email: [email protected] Nifedipine (3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)1,4-dihydropyridine-3,5-dicarboxylate) was developed by the German pharmaceutical company Bayer, most initial studies being performed in the early 1970s. The use of nifedipine and related calcium channel antagonists was much reduced in response to 1995 trials that mortality was increased in patients with coronary artery disease who took nifedipine [16]. This study was a meta-analysis, and demonstrated harm mainly in shortacting forms of nifedipine (that could cause large fluctuations in blood pressure) and at high doses of 80 mg a day and more [15]. Nifedipine is a dihydropyridine calcium channel blocker. Its main uses are as an antianginal (especially in Prinzmetal’s angina) and antihypertensive, although a large number of other indications have recently been found for this agent, such as Raynaud’s phenomenon, premature labor, and painful spasms of the esophagus in cancer and tetanus patients. It is also commonly used for the small subset of pulmonary hypertension patients whose symptoms respond to calcium channel blockers (fig 1). The approved uses for nifedipine are the long-term treatment of hypertension (high blood pressure) and angina pectoris. In hypertension, recent clinical guidelines generally favor diuretics and ACE inhibitors, although calcium channel antagonists, along with thiazide diuretics, are still favored as primary treatment for patients over 55’s [6-8]. Sublingual nifedipine has previously been used in hypertensive emergencies. This was found to be dangerous, and has been abandoned. Sublingual nifedipine causes blood-pressure lowering through peripheral vasodilatation. It can cause an uncontrollable decrease in blood pressure, reflex tachycardia, and a steal phenomenon in certain vascular beds. There have been multiple reports in the medical literature of serious adverse effects with sublingual nifedipine, including cerebral ischemia/ infarction, myocardial infarction, complete heart block, and death. As a result of this, the FDA reviewed all data regarding the safety and efficacy of sublingual nifedipine for hypertensive emergencies in 1995, and concluded that the practice should be abandoned because it was neither safe nor efficacious [9-12]. Experimental researches noticed the relaxing effect of Nifedipine on the guinea pig tracheal smooth muscle constrictor agents comparatively with the prevention of contraction induced by these agents. The aim of this study was to evaluate these considerations in the hydrogen peroxide constrictor effect.