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

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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.",

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

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AU - Risvanis, J.

AU - Hutchins, A. ‐M

AU - Johnston, C. I.

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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

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EFFECTS OF AN ORALLY ACTIVE VASOPRESSIN V₁ RECEPTOR ANTAGONIST

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