Abstract
1 The effect of WAY 405 ((R)-N-(2-methyl-(4-indolyl-1-piperazinyl)ethyl)-N-(2-pyridinyl) cyclohexane carboxamide), a putative 5-HT(1A) receptor antagonist, on cardiovascular function was studied. 2 In anaesthetized rats, the i.v. injection of WAY 405 did not significantly modify basal heart rate nor blood pressure at doses of 1, 3, 10 and 30 microg kg(-1); while the antagonist dose dependently antagonized the 5-HT(1A) receptor agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin)-induced hypotension and bradycardia. 3 WAY 405 antagonized noradrenaline-induced contraction in isolated arteries, with pK(B) values of 6.6+/-0.1, 6.5+/-0.1 and 6.5+/-0.1, for rat tail artery (alpha(1A)-adrenoceptors), rabbit aorta (alpha(1B)-adrenoceptors), and rat aorta (alpha(1D)-adrenoceptors) respectively. 4 The results show that in the control of blood pressure the new compound, WAY 405, behaves as a silent 5-HT(1A) receptor antagonist in the anaesthetized rat, also having low affinity for vascular alpha(1)-adrenoceptors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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8-Hydroxy-2-(di-n-propylamino)tetralin / antagonists & inhibitors
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Aminopyridines / pharmacology*
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Animals
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Aorta / drug effects*
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Aorta / metabolism
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Blood Pressure / drug effects
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Dose-Response Relationship, Drug
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Drug Interactions
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Heart Rate / drug effects
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In Vitro Techniques
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Male
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Norepinephrine / pharmacology
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Piperazines / administration & dosage
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Piperazines / pharmacology*
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Rabbits
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Rats
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Receptors, Adrenergic, alpha-1 / drug effects*
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Serotonin 5-HT1 Receptor Antagonists*
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Serotonin Antagonists / administration & dosage
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Serotonin Antagonists / pharmacology*
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Serotonin Receptor Agonists / pharmacology
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Tail / blood supply
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Vasoconstrictor Agents / pharmacology
Substances
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Aminopyridines
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N-(2-methyl-(4-indolyl-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexane carboxamide
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Piperazines
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Receptors, Adrenergic, alpha-1
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Serotonin 5-HT1 Receptor Antagonists
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Serotonin Antagonists
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Serotonin Receptor Agonists
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Vasoconstrictor Agents
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8-Hydroxy-2-(di-n-propylamino)tetralin
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Norepinephrine