ISSN:
1440-1681
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
1. OPC-21268 and OPC-31260 are newly developed orally active non-peptide vasopressin (AVP) V1 and V2 receptor antagonists, respectively. The effects of the two compounds on human vessels have not been studied.2. The effects of the two compounds on AVP-induced contraction of human internal mammary arteries (IMA) were investigated. Their effects were compared with the peptide V1 and V2 antagonists d(CH2)sSar7AVP (SAVP) and d(CH2)5D-Ileu211eu4AVP (Ileu2 Ileu4AVP), respectively.3. The V1 antagonist OPC-21268 failed to antagonize AVP-induced contraction at low concentrations and potentiated the contraction at higher concentration (3 × 10−-7 mol/L, P〈0.05). It also caused a mild direct contractile effect on IMA. In contrast, the peptide V1 antagonist SAVP potently inhibited the AVP-induced contraction, indicating that functionally constrictor V1 receptors exist in IMA. Both the nonpeptide and peptide V2 antagonists OPC-31260 (3X10−-6 mol/L) and Ileu2Ileu4AVP significantly antagonized the AVP-induced contraction (P〈0.01).4. The AVP-induced contraction was reversed by high concentrations of OPC-31260 (10−-6 mol/L-3×10−-5 mol/L) but not by OPC-21268 (up to 3X 10−-5 mol/L).5. These studies indicate that, in human IMA, OPC-21268 is a partial VI receptor agonist with no V1 receptor antagonist activity, while OPC-31260 is a V1 receptor antagonist. The results also indicate that Ileu2 Ileu4AVP may be a Vl receptor antagonist in humans.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1440-1681.1994.tb02478.x
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