The dopamine receptor agonist Z1046 reduces ischaemia severity in a canine model of coronary artery occlusion

A. Végh, J. Papp, Claudio Semeraro, Zahra Fatehi-Hasanabad, J. Parratt

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Z1046, (S)-6[[6-[[2-(2-methoxyphenoxy)ethyl]amino]propyl]amino]-5,6,7,8- tetra-hydro-1,2-naphtalenediol dihydrochloride, is an agonist at both dopamine D1 and D2 receptors. Since stimulation of dopamine D2 receptors inhibits noradrenaline release, and because cardiac noradrenaline release has been implicated in the genesis of early ischaemia-induced, life-threatening ventricular arrhythmias, the effect of Z1046 has been examined for its effects on coronary artery occlusion in chloralose-urethane anaesthetised mongrel dogs. Z1046 (10 μg kg-1 intravenously or 1 μg kg-1 by local intracoronary injection) decreased heart rate and reduced arterial blood pressure and coronary blood flow, effects prevented by the prior administration of domperidone (40 μg kg-1 i.v.). The ischaemic changes induced by a 25-min occlusion of the left anterior descending coronary artery (including ST-segment elevation and ventricular ectopic activity) were much less marked in those dogs administered Z1046 and survival from the combined ischaemia-reperfusion insult was increased from 7% to 36% (P <0.05) These effects of Z1046 were partly attenuated by domperidone. We conclude that the anti-ischaemic effects of Z1046 are due to inhibition of cardiac sympathetic responses. Studies using rat isolated perfused mesenteric vascular bed preparations subjected to sympathetic nerve stimulation confirmed that Z1046 inhibits synaptic transmission without modifying vascular responses to noradrenaline.

Original languageEnglish
Pages (from-to)203-213
Number of pages11
JournalEuropean Journal of Pharmacology
Volume344
Issue number2-3
DOIs
Publication statusPublished - Mar 5 1998

Fingerprint

Coronary Occlusion
Dopamine Agonists
Canidae
Coronary Vessels
Ischemia
Domperidone
Norepinephrine
Dopamine D2 Receptors
Blood Vessels
Dogs
Dopamine D1 Receptors
Chloralose
Urethane
Z1046
Synaptic Transmission
Reperfusion
Cardiac Arrhythmias
Arterial Pressure
Heart Rate
Injections

Keywords

  • Coronary artery occlusion
  • Dopamine receptor
  • Myocardial ischaemia
  • Ventricular arrhythmia
  • Z1046

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

The dopamine receptor agonist Z1046 reduces ischaemia severity in a canine model of coronary artery occlusion. / Végh, A.; Papp, J.; Semeraro, Claudio; Fatehi-Hasanabad, Zahra; Parratt, J.

In: European Journal of Pharmacology, Vol. 344, No. 2-3, 05.03.1998, p. 203-213.

Research output: Contribution to journalArticle

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