Pharmacology of H 394/84, a dihydropyridine neuropeptide Y Y(1) receptor antagonist, in vivo

European Journal of Pharmacology
R E MalmströmM Sjölander

Abstract

The object of the present paper was to investigate the in vivo pharmacological profile of the dihydropyridine neuropeptide Y Y(1) receptor antagonist 1,4-Dihydro-4-[3-[[[[3-[spiro(indene-4,1'-piperidin-1-yl)]propyl]amino]carbonyl]amino]phenyl]-2,6-dimethyl-3,5-pyridine dicarboxylic acid, dimethylester (H 394/84). The renal vasoconstrictor response to neuropeptide Y in anaesthetized rats was dose-dependently antagonized by H 394/84 (ID(50) value=41+/-4 nmol/kg/min), whereas the renal vascular responses to noradrenaline and angiotensin II were only slightly affected by H 394/84 (500 nmol/kg/min). In pigs pretreated with reserpine and transection of sympathetic nerves (depleted of noradrenaline), H 394/84 dose-dependently antagonized renal and femoral vasoconstrictor responses evoked by sympathetic nerve activation (neuronally released neuropeptide Y) and exogenous neuropeptide Y. Significant inhibition was seen already at 1.0 nmol/kg/min, when plasma levels of the antagonist reached 29+/-4 nM. Around 70% of the antagonism remained 90 min after H 394/84 was given. The disposition of H 394/84 fits a biexponential model with initial and terminal half-lives of 2.6 and 48 min, respectively. H 394/84 (100 nmol/kg/min) did not inhibit v...Continue Reading

References

Oct 15, 1991·European Journal of Pharmacology·A ModinJ M Lundberg
Dec 1, 1991·British Journal of Pharmacology·L Grundemar, R Håkanson
Feb 24, 1968·Nature·R D Stark
Mar 15, 1995·European Journal of Pharmacology·M MousliY Landry
Dec 27, 1994·European Journal of Pharmacology·K RudolfH N Doods
Jun 3, 1996·European Journal of Pharmacology·R E MalmströmJ M Lundberg
Sep 1, 1996·Trends in Pharmacological Sciences·J M LundbergR E Malmström
Sep 1, 1996·Neurochemical Research·M dos S Medeiros, A J Turner
Nov 1, 1996·Naunyn-Schmiedeberg's Archives of Pharmacology·R E Malmström, J M Lundberg
Apr 1, 1997·British Journal of Pharmacology·A BischoffM C Michel
Oct 12, 2000·Journal of Cardiovascular Pharmacology·R E MalmströmJ Weilitz

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Citations

Nov 6, 2002·Clinica Chimica Acta; International Journal of Clinical Chemistry·Antonio P SilvaEric Grouzmann
Jul 11, 2002·European Journal of Pharmacology·Rickard E Malmström
Mar 11, 2003·Experimental Biology and Medicine·Magnus M BerglundDonald R Gehlert
Jul 12, 2007·Chemical Reviews·Jade S BlakeneyDavid P Fairlie
Aug 8, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Angela BischoffMartin C Michel

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