CGMP factors

The regulatory agencies impose certain specific requirements on the formulation and efficacy determination of drags contained in these formulations. For example, the CGMP factors, scale-up and postapproval changes, and dermatological testing for irritation or photosensitivity are some of the specified elements. 

Cyclic GMP is made from GTP by the enzyme gua-nylyl cyclase, which exists in soluble and membrane-bound forms. Each of these isozymes has unique physiologic properties. The atriopeptins, a family of peptides produced in cardiac atrial tissues, cause natriuresis, diuresis, vasodilation, and inhibition of aldosterone secretion. These peptides (eg, atrial natriuretic factor) bind to and activate the membrane-bound form of guanylyl cyclase. This results in an increase of cGMP by as much as 50-fold in some cases, and this is thought to mediate the effects mentioned above. Other evidence links cGMP to vasodilation. A series of compounds, including nitroprusside, nitroglycerin, nitric oxide, sodium nitrite, and sodium azide, all cause smooth muscle re-... 

Fig. 9.1 Nitric oxide mediated inhibition of platelet activation. Abbreviations used NO, nitric oxide EDRF, endothelium-derived relaxing factor GC, guanylyl cyclase PDE, phosphodiesterase cGMP-PK, GMP-dependent protein kinase Raplb, small GTPase Raplb ...

Fig. 3. Mechanisms of vasocontraction and vasorelaxation in endothelial and smooth muscle cells. COX cyclooxygenase, eNOS endothelial nitric oxide synthase, HO-1 heme oxygenase-1, EET epoxyeicosatrienoic acid, EDHF endothelium-derived hyperpolariz-ing factor, PGI2 prostaglandin I2, NO nitric oxide, CO carbon monoxide, PLC phospholipase C, IP3 inositol 1,4,5-trisphosphate, DAG diacylglycerol, ER/SR endo-plasmic/sarcoplasmic reticulum, AC adenylyl cyclase, cAMP cyclic adenosine monophosphate, sGC soluble guanylyl cyclase, cGMP cyclic guanosine monophosphate.

Komori K, Tsujimura A, Takao T, Matsuoka Y, Miyagawa Y, Takada S, Nonomura N, Okuyama A. (2008) Nitric oxide synthesis leads to vascular endothelial growth factor synthesis via the NO/cyclic guanosine 3, 5-monophosphate (cGMP) pathway in human corpus cavemosal smooth muscle cells. J Sex Med 5 1623-1635. 

Quality and documentation aspects in general have become an increasingly important success factor in the fine-chemical business. This is even more true for cGMP production. Because fine chemicals are sold according to stringent specihcations, adherence to constant and strict specifications, at risk because of the batchwise production and the use of the same equipment for... 

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