Vasopressors receptor selectivity

Receptor Pharmacology of Selected Inotropic and Vasopressor Agents Used in Septic Shock1... 

Vasopressin causes vasoconstrictive effects that, unlike adrenergic receptor agonists, are preserved during hypoxia and severe acidosis. It also causes vasodilation in the pulmonary, coronary, and selected renal vascular beds that may reduce pulmonary artery pressure and preserve cardiac and renal function. However, based on available evidence, vasopressin is not recommended as a replacement for norepinephrine or dopamine in patients with septic shock but may be considered in patients who are refractory to catecholamine vasopressors despite adequate fluid resuscitation. If used, the dose should not exceed 0.01 to 0.04 units/min. 

The vasopressor response seen with phenylephrine is particularly strong because it is an a -selective agonist. 02-Agonists actually lower the blood pressure, which is in accord with the role of the 02-receptors in presynaptic inhibition. This inhibition is shown in Figure 10.7a The re-... 

Lebl et al. (180) combined the Thr and the carba substitutions, synthesizing [Thr, deamino-i-carba]oxytocin and [Thr, deainino-6-carba]oxytocm. Although these analogs had slightly reduced potency at the uterus receptor, they were more selective, having much lower vasopressor activity. 

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. 

---