Vasodilators, nitro

Additional studies conducted in this laboratory revealed that NO was responsible for the vascular smooth muscle relaxant effects of several different nitro-vasodilators, and that S-nitrosothiols were intermediates in the intracellular formation of NO (Ignarro et al., 1981). We showed also that NO was a potent inhibitor of human platelet aggregation, and that NO elicited such effects by... 

Key BJ, Keen H Wilkes MP. Reduced responsiveness to nitro-vasodilators following prolonged low dose aspirin administration in man. BrJ Clin Pharmacol (1992) 34,453P-454P. 

Individual vasodilators. Nitrates (p. 120) Ca -antagonists (p. 122). ai-antagonists (p. 90), ACE-inhibitors, ATI -antagonists (p. 124) and sodium nitro-prusside (p. 120) are discussed elsewhere. 

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 vasodilating props of some "new nitro derivs was detd on small animals(Ref 3) ... 

Nitro compounds, in particular aromatic and heterocyclic derivatives, absorb strongly in the near UV. They have properties similar to ketones in their excited state. These compounds are characterized by an unpaired electron in the n0 orbital and thus by a radical character. A typical example of this radical character is the easy intramolecular hydrogen abstraction in nifedipine and related vasodilators (Sch. 7) (18). Another manifestation of the radical character of the nitro group is the rearrangement often observed with nitrated five-membered heterocycles, as in the case of metronidazole (Sch. 8) (19). 

Almost without exception the nitro compounds and nitric acid esters used as explosives are toxic. The degree of toxicity varies widely with the material in question, but most are capable of causing acute distress if taken orally. Nitroglycerin has a small medical use as a vasodilator. 

A theoretically preferable, but often impractical alternative is i.v. infusion of the vasodilator, nitro-prusside (see p. 470). In dissecting aneurysm, vasodilators should not be used unless patients are first p-blocked since any increase in the rate of rise of the pulse stroke is undesirable. Labetalol provides a convenient method of treating all patients within the three circles (except asthmatics), using either oral or parenteral therapy as appropriate. It is not the most effective, however, and should be combined with a long-acting formulation of nifedipine, orally, where further blood pressure reduction is required. 

Interestingly, nitroglycerine ( nitro ) is taken by some who have heart disease. It acts as a vasodilator (dilates the blood vessels) to decrease arterial... 

One of the first compounds prepared (compound 1, Figure 6.13) was indeed found to lower blood pressure in hypertensive rats by a direct peripheral vasodilator mechanism no (3-blocking activity was observed. Optimization of the activity led to the 6-cyano-4-pyrrolidinylbenzopyran (compound 2), which was more than a 100-fold potent than the nitro derivative. The replacement of the pyrrolidine by a pyrrolidinone (which is the active metabolite) produced a 3-fold increase in activity and the optical resolution led to the (-)-3R, 45 enantiomer of cromakalim (BRL 38227) that concentrates almost exclusively the hypotensive activity." " " ... 

The second type of asphyxiants is that which works at the cellular level. Here, they interfere with the mitochondrial cytochrome oxidase s function in the electron transport chain. Because this is the fuel cell for the body, energy production ceases within the cell, with cell death following close behind. The key substance implicated here is cyanide, which is usually found only in a chemical laboratory setting, but can also be a side effect of smoke inhalation. As previously mentioned, hydrogen sulfide and carbon monoxide also have some effect at this site. In addition, azides are cellular asphyxiants. The azides, along with the nitro-ate-ites, are also vasodilators and can cause headaches and hypotension. 

Long needles in regular clusters from ale. mp 106-108. Soluble in ale, in ether insol in water. Explodes on percus si on. Its stability at ordinary temps is such that it may be used commercially, but it is distinctly less stable than nitro-glycerol at 75. Its employ for pharmaceutical prepns is only in admixture with carbohydrate substances in dilutions cor -responding to 1 part of mannitol hexanitrate to 9 or more parts of carbohydrate. In such dilutions mannitol hexanitrate is considered nonexplosive. therap cat Vasodilator. 

---