Vasopressin analogs

Brand Name(s) DDAVP, DDAVP Nasal, DDAVP Rhinal Tube, Minirin, Stimate Chemical Class Arginine vasopressin analog... 

During the past decade, vasopressin has proved beneficial in the treatment of vasodilatory shock states, at least in part by virtue of its Vi agonist activity. Terlipressin (triglycyl lysine vasopressin), a synthetic vasopressin analog that is converted to lysine vasopressin in the body, is also effective. It may have advantages over vasopressin because it is more selective for Vi receptors and has a longer half-life. 

Terlipressin is a vasopressin analog that appears to have similar efficacy to vasopressin with fewer adverse effects. Although this agent is available in other countries, it has never been approved for use in the USA. 

These peptide hormones are among the best-researched active peptide substances. More than 350 oxytocin and vasopressin analogs have been reported in the literature. 

B. Desmopressin is a vasopressin analog. Symptoms are consistent with D1 arising from surgical trauma to the pituitary or hypothalamus and impairment of vasopressin release. The other possibihties would not be alleviated by desmopressin. 

Vasopressin analogs with longer duration of action and selectivity for vasopressin receptor sub-types (Vj Vi. Vj vasopressin receptors, which mediate pressor responses and antidiuretic responses, respectively) have been synthesized. The V -selective agonist, l-deamino-8-D-arginine vasopressin, also called desmopressin (DDAVP), has -3000 times greater antidiuretic-to-vasopressor ratio than vasopressin and is the preferred drug for the treatment of central diabetes insipidus. Substitution of Val for Gin in position 4 further increases the antidiuretic selectivity, and the antidiuretic-to-vasopressor ratio for deamino [Val", D-Arg ]AVP is -11,000 times greater than vasopressin. 

Increasing Vj selectivity has been more difficult than increasing selectivity. Vasopressin receptors in the adenohypophysis that mediate vasopressin-induced ACTH release are neither classical Vj nor Vj receptors. Since the vasopressin receptors in the adenohypophysis appear to share a common signal-transduction mechanism with classical Vj receptors, and since many vasopressin analogs with vasoconstrictor activity release ACTH, Vj receptors have been subclassified into Vj (vascular/hepatic) and Vjj (pituitary) receptors. Vjj receptors also are called Vj receptors. Vasopressin analogs that are selective agonists for Vj and Vjj receptors have been synthesized but are not available clinically. 

In Uppsala, J. Porath and P. Flodin developed an extremely important method for the separation of peptides and proteins gel permeation chromatography with crosslinked dextran (Sephadex). One of Porath s former associates, Ulf Ragnarsson contributed with innovative modifications to the solid phase method of peptide synthesis and in more recent years introduced the principle of complete protection of the amine function by diacylation. Another Porath student, Gunnar Lindeberg, explored the properties of vasopressin analogs. 

H. Brondsted, H.M. Nielsen, L. Hovgaard, Drug-delivery studies in caco-2 monolayers. 3. intestinal transport of various vasopressin analogs in the presence of lysophosphatidylcholine. Int. J. Pharm. 114, 151-157 (1995)... 

S. Lundin, P. Artursson, Absorption of a vasopressin analog, ldeamino-8-D-arginine-vasopressin (DDAVP), in a human intestinal epithelial-cell line, CaCO-2. Int. J. Pharm. 64, 181-186 (1990)... 

Lutz, W. H. Londowski, J. M. Kumar, R. The synthesis and biological activity of four novel fluorescent vasopressin analogs. J. Biol. Chem. 1990, 265,4657-4663. 

---