Sodium nitroprusside release

SM Sphingomyelin SNAP S-Nitroso-N-acetylpenicillamine SNP Sodium nitroprusside SOD Superoxide dismutase SOM Somatostatin also knotm as somatotrophin release-inhibiting factor... 

Sodium nitroprusside (SNP), which is also known as Nipruss or Nipride to medical practitioners, was the first iron nitrosyl complex, prepared as far back as 1850 by Playfair [40]. The hypotensive property of SNP was first demonstrated by Johnson [41] in 1929. It was shown that application of a moderate dose of SNP reduces the blood pressure of a severely hypertensive patient without any side effect [42]. Since that time considerable research has been carried out to understand the mode of action of nitroprusside and its metabolic fate. SNP is now regarded as a potent vasodilator that causes muscle relaxation by releasing NO which activates the cytosolic isozyme of guanylyl cyclase [43-46]. 

Although its mode is uncertain, sodium nitroprusside (SNP) is one of the most valuable vasodilators. Its use in clinical practice is suspect as the cyano-ligands render cyanide poisoning a possibility. However for ex vivo experiments this consideration is less important but the possibility of some biological action due to these ions remains. The mechanism by which SNP acts as a vasodilator is not fully understood. With the discovery of a physiological role for NO there has been renewed interest in mechanistic studies of reactions involving SNP and a re-examination of studies of SNP undertaken before 1987. So far, only one simple reaction leading to the release... 

The therapeutic effects of sodium nitroprusside depend on release of nitric oxide which relaxes vascular muscle. Sodium nitroprusside is best formulated as a nitrosonium (NO+) complex. Its in vivo activation is probably achieved by reduction to [Fe(CN)5NO]3, which then releases cyanide to give [Fe(CN)4NO]2, which in turn releases nitric oxide and additional CN to yield aquated Fe(II) species and [Fe(CN)6]4 (502). There are problems associated with its use, namely reduced activity due to photolysis (501) and its oxidative breakdown due to the action of an activated immune system (503), both of which release cyanide from the low-spin d6 iron complex. 

Hada J, Kaku T, Jiang MH, Morimoto K, Hayashi Y. 2003. Inhibition of high K -evoked gamma-aminobutyric acid release by sodium nitroprusside in rat hippocampus. Eur J Pharmacol 467(1-3) 119-123. 

Sodium nitroprusside is the only clinically used metal complex of NO, so that its reactions provide an indication of the types of reactivity that metallonitrosyl complexes might be expected to have in physiological environments (see Fig. 1). The in vivo activation of nitroprusside depends on its reduction to [Fe(CN)5NO], which then releases cyanide to give [Fe(CN)4NO] which in turn releases NO and additional CN to yield Fejl,) and [Fe(CN)g] [75]. [Fe(CN)5(NO)] is paramagnetic (g, = 1.9993, g, = 1.9282, g = 2.008,... 

Sodium nitroprusside (SNP) is both a venous and an arterial vasodilator. An important part of its vasodilator action is caused by the release of nitric oxide (NO), similarly as for the organic nitrates. SNP can only be administered via the intravenous route. It is a rapidly and short acting vasodilator. It has been used in the treatment of hypertensive emergencies and in the management of myocardial ischaemia. In spite of its vasodilator action it hardly influences heart rate, in contrast to hydralazine and minoxidil. The dosage of SNP should not be higher than 3 pg/kg/min within 48 h, in order to avoid the rise of cyanide ions and thiocyanate in the blood. 

Sodium nitroprusside is a powerful parenterally administered vasodilator that is used in treating hypertensive emergencies as well as severe heart failure. Nitroprusside dilates both arterial and venous vessels, resulting in reduced peripheral vascular resistance and venous return. The action occurs as a result of activation of guanylyl cyclase, either via release of nitric oxide or by direct stimulation of the enzyme. The result is increased intracellular cGMP, which relaxes vascular smooth muscle (Figure 12-2). 

Sodium nitroprusside was first prepared and investigated in the middle of the nineteenth century, and a comprehensive summary of the earlier chemical investigations has been published (17). Up to 1910-1930, the addition reactions of bases to NP were explored, involving the characterization of colored intermediates (e.g., with SH-, SR-, and SO3 ), useful for analytical purposes. The hypotensive action of NP was first demonstrated in 1929, and a considerable research effort has attempted to establish the mode of action of NP and its metabolic fate. Questions still arise on the mechanism of NO release from NP in the biological fluids, and we refer to them below. New accounts dealing with modern structural and reactivity issues associated with the coordination of nitrosyl in NP and other complexes have appeared (18-20). From the bioinorganic and environmental viewpoint, nitrosyl iron complexes have been studied with... 

Molsidomine itself is inactive. After oral intake, it is slowly converted into an active metabolite, linsidomine. The differential effectiveness in arterial vs. venous beds is less evident compared to the drugs mentioned above. Moreover, development of nitrate tolerance is of less concern. These differences i n activi ty profi le appear to reflect a different mechanism of NO release. The same applies to the following sodium nitroprusside. 

An ethical drug that may also cause cyanide poisoning in overdose is the potent vascular smooth-muscle relaxant sodium nitroprusside. Although nitroprusside is related chemically to ferricyanide, unlike the latter it penetrates into erythrocytes and reacts with hemoglobin to release its cyanide (Smith and Kruszyna, 1974). Fortunately, the therapeutic margin for nitroprusside appears to be quite large. 

The release of cyanide and ferricyanide ions in photodecomposed solutions of sodium nitroprusside is considered to be a great health hazard (15). One of the photoproducts of benzydamine hydrochloride is reported to be responsible for its reported phototoxic effect (16). 

Compounds that release cyanide spontaneously, by thermal decomposition, or by chemical reaction, such as cyanogen, cyanogen bromide, cyanogen chloride, calcium cyanide, acetonitrile, laetrile, amygdalin, lethane, thanate, sodium nitroprusside, cassava root... 

Ru(NH3)4P(OEt)3(NO)](PF6)3 exhibits reduced toxicity and similar hypertensive activity compared with sodium nitroprusside, which is used to treat cardiovascular disorders in animal studies. This property is due to the strong trans effect of the P(OEt)3 ligand, which is responsible for the release of the NO group [57]. With trons-[RuCl(cyclam)(NO)](PF6)2, prolonged blood pressure reduction was observed (cyclam= 1,4,8,11-tetraazacyclotetradecane) [58]. 

Diazoxide is a parenteral, rapid, and direct-acting vasodilating antihypertensive used in hypertensive emergencies. An IV injection can drop blood pressure by as much as 80 mmHg in 5 minutes. Unlike sodium nitroprusside, however, venous dilation is not part of its mechanism. Chemically it is a benzothiadiazide without the sulfamoyl function at the 7 position (see diuretics). In fact, diazoxide is not a diuretic. Chronic use of diazoxide reflexly increases renin release, which actually counteracts the antihypertensive effect of the drug by expanding the volume of circulating fluid. 

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