Vasopressin derivatives

To ensure a reasonably long-lasting local effect with minimal systemic action, a vasoconstrictor (epinephrine, less frequently norepinephrine or vasopressin derivatives) is often co-administered in an attempt to confine the drug to its site of action. As blood Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms... 

Antacids, H2-receptor antagonists Propranolol and its derivatives Vasopressin derivatives Somatostatin or octreotide Fresh plasma... 

Willebrand s sjmdrome (18). This potential hemorrhagic complication is treatable, since tjrpe 1 von Willebrand s syndrome can be controlled with the vasopressin derivative desmopressin. 

Chemical shift target functions proved their power especially in the refinement of smaller peptides as for example a vasopressin derivative.Using only traditional constraints, this cyclic peptide switched in MD simulations between two conformations. h chemical shift constraints forced the structure into a single conformation that not only fits the chemical shift constraints well but also satisfies the NOE constraints better than in their absence. Despite the fact that the accuracy of this type of chemical shift calculation for protons is still relatively low (about 0.25 ppm), chemical shift constraints can significantly reduce the conformational space allowed for the structures. 

In humans, the hypothalamic-derived protein and the hormone noncovalent complexes are packaged in neurosecretory granules, then migrate along axons at a rate of 1 4 mm/h until they reach the posterior pituitary where they are stored prior to release into the bloodstream by exocytosis (67). Considerable evidence suggests that posterior pituitary hormones function as neurotransmitters (68) vasopressin acts on the anterior pituitary to release adrenocorticotropic hormone [9002-60-2] (ACTH) (69) as well as on traditional target tissues such as kidneys. Both hormones promote other important central nervous system (CNS) effects (9,70). 

Vasopressin (Rtressin Synthetic) and its derivatives, namely lypressin (Diapid) and desmopressin (DDAVP), regulate the reabsorption of water by the kidneys. Vasopressin is secreted by the pituitary when body fluids must be conserved. An example of this mechanism may be seen when an individual has severe vomiting and diarrhea with little or no fluid intake. When this and similar conditions are present, die posterior pituitary releases the hormone vasopressin, water in die kidneys is reabsorbed into die blood (ie, conserved), and die urine becomes concentrated. Vasopressin exhibits its greatest activity on die renal tubular epithelium, where it promotes water resoqition and smooth muscle contraction throughout die vascular bed. Vasopressin has some vasopressor activity. 

Vasopressin and its derivatives are used in die treatment of diabetes insipidus, a disease resulting from die failure of the pituitary to secrete vasopressin or from surgical removal of die pituitary. Diabetes insipidus is characterized by marked increase in urination (as much as 10 L in 24 hours) and excessive tiiirst by inadequate secretion of die antidiuretic hormone or vasopressin. Treatment with vasopressin therapy replaces die hormone in the body and restores normal urination and thirst Vasopressin may also be used for die prevention and treatment of postoperative abdominal distention and to dispel gas interfering with abdominal roentgenography. 

The dosage of vasopressin or its derivatives may require periodic adjustments. After administration of die drug, die nurse observes die patient every 10 to 15 minutes for signs of an excessive dosage (eg, blanching of the skin, abdominal cramps, and nausea). If tiiese occur, die nurse reassures die patient that recovery from tiiese effects will occur in a few minutes. 

Additiona medication Additiona medication to be used rareiy under specie circumstances Inciude Giucagon, atropine derivatives, dopamine, vasopressin (these drugs should be given by experienced physicians in the adequate setting)... 

The search for an effective non-peptide oxytocin antagonist has become a major goal of a number of pharmaceutical companies because of the poor pharmacokinetic properties and especially the lack of oral bioavailability associated with peptidic antagonists. Early research in this field was dominated by Merck, but in recent years significant research efforts at GlaxoSmithKline and Serono have been published. A number of other companies, notably Sanofi-Aventis, Yamanouchi and Wyeth, have had a major presence in vasopressin receptor research and oxytocin is frequently included in patent claims for the molecules. Occasionally, oxytocin-selective compounds have been reported, usually derived by adaptation of the vasopressin antagonist template. 

Rich, D.H., Gesellchen, P.D., Tong, A., Cheung, A., and Buckner, C.K. (1975) Alkylating derivatives of amino acids and peptides. Synthesis of N-maleoyl amino acids, l-[N-maleoylglycyl-cysteinyl]-oxytocin and l-[N-maleoyl-ll-aminoundecanoyl-cysteinyl]-oxytocin. Effects on vasopressin stimulated water loss from isolated toad bladder. J. Med. Chem. 18,1004-1010. 

ADH, a nonapeptide, released from the posterior pituitary gland promotes re-absorption of water in the kidney. This response is mediated by vasopressin receptors of the V2 subtype. ADH enhances the permeability of collecting duct epithelium for water (but not for electrolytes). As a result, water is drawn from urine into the hyperosmolar inter-stitium of the medulla. Nicotine augments (p. 110) and ethanol decreases ADH release. At concentrations above those required for antidiuresis, ADH stimulates smooth musculature, including that of blood vessels ( vasopressin ). The latter response is mediated by receptors of the Vi subtype. Blood pressure rises coronary vasoconstriction can precipitate angina pectoris. Lypres-sin (8-L-lysine vasopressin) acts like ADH. Other derivatives may display only one of the two actions. 

Nephrogenic diabetes insipidus is due to resistance to action of vasopressin, and therefore DDAVP is not indicated, but some benefit may be gained by using thiazide diuretics or chlorpropamide. The syndrome of inappropriate antidiuretic hormone (SIADH) can be treated by using the antibiotic derivative demeclocycline to induce a state of vasopressin resistance and partial nephrogenic diabetes insipidus. 

Platelet-derived growth factor (PDGF) Serotonin [5-HT-lc] Thyrotropin-releasing hormone (TRH) Vasopressin... 

The cq receptors are activated not only by catecholamines but also by the hormones vasopressin and angiotensin n. Binding of these hormones to a, receptors induces a complex response that involves rapid hydrolysis of phosphatidylinositol derivatives and release of Ca2+ into die cytoplasm, and of diacylglycerols into the lipid bilayer of the membrane. The response is mediated by another G protein called Gq.27 1 275 When this G protein is activated it induces the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdInsP2), a normal minor component of the lipid bilayer, by phospholipase C (phosphoinositidase C).265,276 281... 

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