Central vasopressin V1-receptors mediate indomethacin-induced antipyresis in rats

Central microinjection or infusion of an arginine vasopressin (AVP) V1-receptor antagonist within the brain of the conscious, unrestrained, and febrile rat inhibited or abolished the antipyretic effects of peripherally administered indomethacin (Indo). The degree of Indo-induced antipyresis was determined by 2-h thermal indexes (degree C.h) calculated from the time of Indo injection. Microinjection of saline or V1-receptor antagonist within the ventral septal area (VSA) of the rat brain immediately followed by intraperitoneal Indo evoked antipyretic responses of -1.63 +/- 0.17 and -0.24 +/- 0.09 degrees C.h, respectively (P less than 0.01). Infusion of the VSA with saline or V1-receptor antagonist before and after Indo resulted in thermal indexes of -1.35 +/- 0.16 and 0.13 +/- 0.30 degree C.h, respectively (P less than 0.01). Central microinjection of a V2-receptor antagonist did not significantly effect Indo-induced antipyresis compared with paired saline controls. Neither saline nor the V1-receptor antagonist affected nonfebrile body temperature when microinjected into the VSA. These data indicate the importance of AVP V1-receptors within the VSA in mediating the potent fever-reducing properties of the antipyretic drug Indo. Furthermore, these data call into question whether prostaglandin synthesis inhibition is a sufficient explanation of drug-induced antipyresis.

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A new selective, and sensitive method for the determination of lixivaptan, a vasopressin 2 (V2)-receptor antagonist, in mouse plasma and its application in a pharmacokinetic study

Open Chemistry ◽

10.1515/chem-2018-0063 ◽

2018 ◽

Vol 16 (1) ◽

pp. 614-620

Author(s):

Haitham Alrabiah ◽

Mohammed Abunassif ◽

Sabry Attia ◽

Gamal Abdel-Hafiz Mostafa

Keyword(s):

Receptor Antagonist ◽

Pharmacokinetic Study ◽

Limit Of Detection ◽

Internal Standard ◽

Hplc Method ◽

Maximum Plasma ◽

Mouse Plasma ◽

V2 Receptor ◽

V2 Receptor Antagonist

AbstractA new, selective and sensitive HPLC method for the determination of lixivaptan, an oral selective vasopressin 2 (V2)-receptor antagonist, was investigated and validated. A Waters symmetry C18 column was used as a stationary phase in isocratic elution mode using a mobile phase composed of KH2PO4 (100 mM)-acetonitrile (40: 60, v/v) at a flow rate of 1.5 mL min-1. Diclofenac was used as the internal standard (IS). Lixivaptan and the IS were extracted from plasma by protein precipitation and were detected at 260 nm. Lixivaptan and diclofenac were eluted at 3.6 and 6.2 min, respectively. The developed method showed good linearity over the calibration range of 50 -1000 ng mL-1 with a lower limit of detection of 16.5 ng mL-1. The extraction percentage of lixivaptan in the mouse plasma was in the range of 88.88 - 114.43%, which indicates acceptable extraction. The aforementioned method was validated according to guidelines of the International Council on Harmonization (ICH). The intra- and inter-day coefficients of variation did not exceed 5.5%. This method was presented to be simple, sensitive, and accurate and was successfully adapted in a pharmacokinetic study of the profile of lixivaptan in mouse plasma. A mean maximum plasma concentration of lixivaptan of 113.82 ng mL-1 was achieved in 0.5 h after oral administration of a 10 mg kg-1 dose in mouse as determined using the developed method.

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Arginine vasopressin produces renal vasodilation via V2 receptors in conscious dogs

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1993.265.4.r934 ◽

1993 ◽

Vol 265 (4) ◽

pp. R934-R942 ◽

Cited By ~ 11

Author(s):

M. Naitoh ◽

H. Suzuki ◽

M. Murakami ◽

A. Matsumoto ◽

A. Ichihara ◽

...

Keyword(s):

Cardiac Output ◽

Receptor Antagonist ◽

Arginine Vasopressin ◽

Statistical Significance ◽

Conscious Dogs ◽

Receptor Blockade ◽

Vasodilatory Response ◽

V2 Receptor ◽

Plasma Arginine ◽

V2 Receptor Antagonist

In conscious dogs, 36-h water deprivation induced a significant increase in renal blood flow (RBF) with elevation of the plasma arginine vasopressin (AVP) concentration to 9.6 +/- 1.8 pg/ml. To simulate such a condition, a mild elevation of plasma AVP was produced by infusing AVP intravenously at a dose of 0.1 ng.kg-1.min-1 for 20 min. The plasma AVP concentration then increased to 6.8 +/- 0.7 pg/ml. This dose of AVP increased the RBF by 21.7 +/- 2.6% and decreased the renal vascular resistance by 18.1 +/- 2.3% without significant changes in mean arterial pressure, cardiac output, or heart rate. The mechanism of this renal vasodilatory action was examined using newly developed, orally effective, selective AVP antagonists OPC-21268 (a V1-receptor antagonist) and OPC-31260 (a V2-receptor antagonist). In 36-h water-deprived dogs, V2-receptor blockade with OPC-31260 significantly decreased the RBF by 20.5 +/- 2.6% without significant changes in cardiac output. The exogenous AVP-induced renal vasodilatory response tended to be augmented when V1 receptors were blocked by pretreatment with OPC-21268, but the change did not achieve statistical significance. On the other hand, V2-receptor blockade by either pretreatment with OPC-31260 or simultaneous infusion of OPC-31260 inhibited this vasodilatory response. Furthermore, intravenous infusion of 1-desamino-8-D-arginine vasopressin (DDAVP) at a dose of 0.3 ng.kg-1 x min-1 for 20 min significantly increased the RBF by 36.5 +/- 1.7%, and this DDAVP-induced renal vasodilation was inhibited by simultaneous infusion of V2-receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

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