Vasodilators agents

Mannich condensation of the primary amine corresponding to ephedrine (32) with formaldehyde and m-methoxyacetophenone yields oxyfedrine (33), this agent retains the vasodilating activity of ephedrine and is in fact denoted a coronary vasodilating agent. 

Alkoxyhexadehydroyohimbanes (618) and 17-alkoxydecadehydroyohim-banes (619) have analgesic and hypotensive activities (356, 357). On the other hand, 16,17,18-trialkoxyhexadehydroyohimbanes (620) are useful as hypotensive and vasodilating agents (358). 

In the United States, compound RGW-2938 (47) has been developed as a selective positive inotropic agent its synthesis and pharmacological actions have been reviewed [161]. Related compounds, in which the dihydro-pyridazinone system is replaced by a benzoxazinyl system instead of the quinazoline system, have recently been studied in India and in the United States [162,163]. From this series, bemoradan (48) was found to be a very potent orally active, long-acting inotropic vasodilator agent in canine models (i.v. ED5o = 5.4 //g/kg 24h duration of action) [163]. 

There are numerous patents claiming 3-hydrazinopyridazine derivatives with amino-substituted alkoxy side-chains at C-6 as ff-blocking vasodilating agents [188,286-293]. Other 3-hydrazinopyridazine-derived antihypertensive agents are covered by patents [294-301], or described in the literature [302 306]. It should be noted that with structurally very simple hydrazino-pyridazines like 6-hydrazino-3-pyridazinecarboxamide (hydracarbazine, 2105 TH CAS 3164-47-9), antihypertensive activity has been observed. 

Another khellin-inspired benzofuran is the cardiotonic and vasodilating Agent, benfurodil (84)... 

A still different scheme is used for the preparation of the benzimidazole buterizine (74). Alkylation of benzhydrylpiperazine with substituted benzyl chloride 70 gives the intermediate 7U Nucleophilic aromatic displacement on this compound by means of ethyl amine leads to reduction of the nitro group then gives the diamine T. Treatment of that with the orthoformate ester of pentanoic acid serves to form the imidazole ring. There is thus obtained the peripheral vasodilating agent buteri zi ne (74). ... 

The mechanism of action of these drugs is not completely understood. However, it is very likely that they inhibit cellular phosphodiesterase of the myocardium, which leads to an elevation in the cellular level of cyclic AMP, which in turn facihtates contraction of myocardial cells. It is clear that these drags are not 8-adrenoreceptor antagonists, and that their effect is not mediated by inhibition of (Na -K+) ATPase. They simultaneously increase the flow of calcium ions into the cell. They are used for short-term control of patients that inadequately react to cardiac glycosides, diuretics, and coronary vasodilating agents. 

Over the past 10 years, coronary vasodilating agents have been reconunended as the primary compounds for treating cardiac insufficiency. 

These drugs were developed as coronary vasodilating agents and were used for that purpose for some time, until it was discovered that they inhibit the contractile effect of calcium on smooth musculature and cardiac muscle, and that they affect calcium channels on the cell surface that permit calcium ions to enter. At first, they were called calcium antagonists however, later on this class of compounds was given the preferred name of calcium channel blockers. 

Dipiridamol is known as a coronary vasodilating agent, although it also possesses specific antiaggregant activity. It is used for preventing thrombo-formation after cardiac valve replacement in combination with warfarin. The mechanism of dipiridamoTs antiaggregant action is not completely clear, and its efficacy is questionable. 

Verapamil and a few newer dmgs of this category are vasodilator agents, which in addition impair AV conduction, reduce heart rate and cardiac contractile force. Verapamil was initially developed for the treatment of supraventricular tachycardia and it continues to be an important drug for the management of this condition, also postoperatively. Verapamil is the CA of choice in the management of hypertrophic cardiomyopathy. Verapamil is also used in the treatment of stable angina and, less frequently, essential hypertension. 

Because of the wide range of specificity of sulpiride and other substituted benzamides, it is possible to administer these drugs intravenously and differentiate renal or mesenteric vasodilation produced by DA from non-specific vasodilating agents such as bradykinin (18,Jj)). However, we disagree with Shepperson et al 20) who estimated the relative potency of less specific antagonists by the intravenous route. 

Angiotensin II, itself a potent hypertensive agent, also stimulates the release of a second hypertensive agent, aldosterone. In addition, ACE catalyzes the cleavage of the nonapeptide vasodilating agent, bradykinin (not shown). Therefore an ACE inhibitor was seen to have the potential to limit three hypertensive actions. This premise was validated by in vivo results with teprotide, a peptide inhibitor of... 

Kereiakes D, Chatterjee K, Parmley WW, Atherton B, Curran D, Kereiakes A, Spangenberg R. Intravenous and oral MDL 17043 (a new inotrope-vasodilator agent) in congestive heart failure hemodynamic and clinical evaluation in 38 patients. I Am Coll Cardiol I984 4(5) 884-9. 

Coffman JD, Cohen RA. Intra-arterial vasodilator agents to reverse human finger vasoconstriction. Clin Pharmacol Ther 1987 41(5) 574-9. 

Chemical/Pharmaceutical/Other Class Hypotensive agent Vasodilating agent Chemical Formula C9H15N5O Chemical Structure ... 

Avoid vasodilating agents such as spicy food or alcohol. 

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