Terlipressin, a vasoactive prodrug recommended in hepatorenal syndrome, is an agonist of human V1, V2 and V1B receptors: Implications for its safety profile

Abstract

Terlipressin is a non-selective vasopressin analogue, exhibiting intrinsic agonist properties. Its full V2 receptor agonism may result in renal effects potentially aggravating water retention and hyponatremia of cirrhosis.

In vitro binding and receptor-mediated activity of terlipressin at vasopressin receptors V₁ and V₂

“…The mean binding affinity of terlipressin for human V 1 receptors (1229 nM) was about 120-fold less than the binding affinity of LVP (10 nM); about a 700-fold difference in terlipressin (852 nM) versus LVP binding (1.2 nM) was observed at rat V 1 receptors. 11 Mean maximal cell activation with terlipressin, as measured by intracellular calcium mobilization, was 48% at human V 1 receptors and 66% at rat V 1 receptors versus 100% with LVP. 11 The selectivity of terlipressin for V 1 receptors was 1.9-fold higher than that for V 2 receptors compared with the 6.3-fold higher selectivity observed in our study.…”

“… 11 Mean maximal cell activation with terlipressin, as measured by intracellular calcium mobilization, was 48% at human V 1 receptors and 66% at rat V 1 receptors versus 100% with LVP. 11 The selectivity of terlipressin for V 1 receptors was 1.9-fold higher than that for V 2 receptors compared with the 6.3-fold higher selectivity observed in our study. This difference may be a reflection of the different cell lines utilized for competitive binding assays (rat and human vascular smooth muscle cells versus CHO cells, respectively) in the two studies.…”

“…Our results support findings from previously reported studies and provide additional evidence regarding the pharmacologic properties of terlipressin. 2 , 11 , 12 Colson et al, 11 using vascular smooth muscle cells isolated from rat aorta and human uterine artery, found that the relative binding affinity (K i [nM]) of LVP, AVP, and terlipressin for human and rat V 1 receptors was AVP>LVP>>terlipressin. The mean binding affinity of terlipressin for human V 1 receptors (1229 nM) was about 120-fold less than the binding affinity of LVP (10 nM); about a 700-fold difference in terlipressin (852 nM) versus LVP binding (1.2 nM) was observed at rat V 1 receptors.…”

Juvenile-onset gout and adipsic diabetes insipidus: A case report and literature review

“…However, the urate clearance rate significantly increased when coupled with terlipressin (triglycyl-lysine vasopressin), a selective V1 receptor agonist. 16 , 17 Therefore, the lack of V1 receptor stimulation could explain why patients with CDI present with hyperuricemia. Although the mechanism remains unclear, some hypotheses have been proposed.…”

Terlipressin‐induced modifications of Doppler ultrasound signals of systemic arteries in preterm infants with vasoactive‐resistant patent ductus arteriosus: A pilot study

“…26,27 TP-induced modifications of the Doppler blood flow signal in the renal artery (Figure 2, bottom) support the hypothesis that TP may enhance renal perfusion by increasing mean arterial blood pressure and renal vascular dilation in the ELBW infants with hs-PDA, as previously theorized for arginine vasopressin (AVP). 28 TP is a synthetic analogue of AVP presented as a specific vasopressin 1a receptor (V1a-R) agonist, although its full V1b-R and V2-R agonism 29 has been recently suggested. We suppose that TP may preserve glomerular perfusion and filtration in infants with hs-PDA by the complex interplay between selective V1-R stimulation of the extrarenal vasculature, vasodilation of the afferent arterioles, and intrarenal shift of blood flow to the cortex.…”