EFFECTS OF AN ORALLY ACTIVE VASOPRESSIN V1 RECEPTOR ANTAGONIST

L. M. Burrell; P. A. Phillips; J. Stephenson; J. Risvanis; A. ‐M Hutchins; C. I. Johnston

doi:10.1111/j.1440-1681.1993.tb01713.x

EFFECTS OF AN ORALLY ACTIVE VASOPRESSIN V₁ RECEPTOR ANTAGONIST

L. M. Burrell
, P. A. Phillips
, J. Stephenson
, J. Risvanis
, A. ‐M Hutchins
, C. I. Johnston

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

1. This paper reports on the in vitro and in vivo characteristics of a non‐peptide vasopressin V₁ receptor antagonist 1‐{1‐[4‐(3‐acetylaminopropoxy)benzoyl]‐4‐piperidyl}‐3,4‐dihydro‐2(1H)‐quinolinone (OPC‐21268). 2. OPC‐21268 caused a concentration‐dependent displacement of the selective V₁ receptor antagonist radioligand, [¹²⁵I]‐[d(CH₂)₅, sarcosine⁷]AVP from vasopressin V₁ receptors in rat liver and kidney membranes, inhibitory concentration of 50% (IC₅₀) 4 ± 10‐⁸, 0.3 mol/L liver and 1.5 ± 10‐⁸, 0.2 mol/L kidney. OPC‐21268 had little effect on the selective V₂ antagonist radioligand [³H]desGly‐NH₂⁹‐d(CH₂)₅[d‐Ileu², Ileu⁴]AVP binding to V₂ receptors in renal membranes (IC₅₀ > 10‐⁴ mol/L). 3. After oral administration to rats, OPC‐21268 was an effective V₁ antagonist to both liver and kidney V₁ receptors, in a dose‐dependent manner. 4. These studies confirm that OPC‐21268 is a potent non‐peptide, orally effective V₁ vasopressin receptor antagonist.

Original language	English
Pages (from-to)	388-391
Number of pages	4
Journal	Clinical and Experimental Pharmacology and Physiology
Volume	20
Issue number	5
DOIs	https://doi.org/10.1111/j.1440-1681.1993.tb01713.x
Publication status	Published - May 1993
Externally published	Yes

Keywords

OPC‐21268
vasopressin antagonist
vasopressin receptor.

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title = "EFFECTS OF AN ORALLY ACTIVE VASOPRESSIN V1 RECEPTOR ANTAGONIST",

abstract = "1. This paper reports on the in vitro and in vivo characteristics of a non‐peptide vasopressin V1 receptor antagonist 1‐\{1‐[4‐(3‐acetylaminopropoxy)benzoyl]‐4‐piperidyl\}‐3,4‐dihydro‐2(1H)‐quinolinone (OPC‐21268). 2. OPC‐21268 caused a concentration‐dependent displacement of the selective V1 receptor antagonist radioligand, [125I]‐[d(CH2)5, sarcosine7]AVP from vasopressin V1 receptors in rat liver and kidney membranes, inhibitory concentration of 50\% (IC50) 4 ± 10‐8, 0.3 mol/L liver and 1.5 ± 10‐8, 0.2 mol/L kidney. OPC‐21268 had little effect on the selective V2 antagonist radioligand [3H]desGly‐NH29‐d(CH2)5[d‐Ileu2, Ileu4]AVP binding to V2 receptors in renal membranes (IC50 > 10‐4 mol/L). 3. After oral administration to rats, OPC‐21268 was an effective V1 antagonist to both liver and kidney V1 receptors, in a dose‐dependent manner. 4. These studies confirm that OPC‐21268 is a potent non‐peptide, orally effective V1 vasopressin receptor antagonist.",

keywords = "OPC‐21268, vasopressin antagonist, vasopressin receptor.",

author = "Burrell, \{L. M.\} and Phillips, \{P. A.\} and J. Stephenson and J. Risvanis and Hutchins, \{A. ‐M\} and Johnston, \{C. I.\}",

year = "1993",

month = may,

doi = "10.1111/j.1440-1681.1993.tb01713.x",

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AU - Burrell, L. M.

AU - Phillips, P. A.

AU - Stephenson, J.

AU - Risvanis, J.

AU - Hutchins, A. ‐M

AU - Johnston, C. I.

PY - 1993/5

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N2 - 1. This paper reports on the in vitro and in vivo characteristics of a non‐peptide vasopressin V1 receptor antagonist 1‐{1‐[4‐(3‐acetylaminopropoxy)benzoyl]‐4‐piperidyl}‐3,4‐dihydro‐2(1H)‐quinolinone (OPC‐21268). 2. OPC‐21268 caused a concentration‐dependent displacement of the selective V1 receptor antagonist radioligand, [125I]‐[d(CH2)5, sarcosine7]AVP from vasopressin V1 receptors in rat liver and kidney membranes, inhibitory concentration of 50% (IC50) 4 ± 10‐8, 0.3 mol/L liver and 1.5 ± 10‐8, 0.2 mol/L kidney. OPC‐21268 had little effect on the selective V2 antagonist radioligand [3H]desGly‐NH29‐d(CH2)5[d‐Ileu2, Ileu4]AVP binding to V2 receptors in renal membranes (IC50 > 10‐4 mol/L). 3. After oral administration to rats, OPC‐21268 was an effective V1 antagonist to both liver and kidney V1 receptors, in a dose‐dependent manner. 4. These studies confirm that OPC‐21268 is a potent non‐peptide, orally effective V1 vasopressin receptor antagonist.

AB - 1. This paper reports on the in vitro and in vivo characteristics of a non‐peptide vasopressin V1 receptor antagonist 1‐{1‐[4‐(3‐acetylaminopropoxy)benzoyl]‐4‐piperidyl}‐3,4‐dihydro‐2(1H)‐quinolinone (OPC‐21268). 2. OPC‐21268 caused a concentration‐dependent displacement of the selective V1 receptor antagonist radioligand, [125I]‐[d(CH2)5, sarcosine7]AVP from vasopressin V1 receptors in rat liver and kidney membranes, inhibitory concentration of 50% (IC50) 4 ± 10‐8, 0.3 mol/L liver and 1.5 ± 10‐8, 0.2 mol/L kidney. OPC‐21268 had little effect on the selective V2 antagonist radioligand [3H]desGly‐NH29‐d(CH2)5[d‐Ileu2, Ileu4]AVP binding to V2 receptors in renal membranes (IC50 > 10‐4 mol/L). 3. After oral administration to rats, OPC‐21268 was an effective V1 antagonist to both liver and kidney V1 receptors, in a dose‐dependent manner. 4. These studies confirm that OPC‐21268 is a potent non‐peptide, orally effective V1 vasopressin receptor antagonist.

KW - OPC‐21268

KW - vasopressin antagonist

KW - vasopressin receptor.

UR - https://www.scopus.com/pages/publications/0027253652

U2 - 10.1111/j.1440-1681.1993.tb01713.x

DO - 10.1111/j.1440-1681.1993.tb01713.x

M3 - Article

C2 - 8391950

AN - SCOPUS:0027253652

SN - 0305-1870

VL - 20

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JO - Clinical and Experimental Pharmacology and Physiology

JF - Clinical and Experimental Pharmacology and Physiology

IS - 5

ER -

EFFECTS OF AN ORALLY ACTIVE VASOPRESSIN V₁ RECEPTOR ANTAGONIST

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