Document Detail

The dopamine receptor agonist Z1046 reduces ischaemia severity in a canine model of coronary artery occlusion.
MedLine Citation:
PMID:  9600656     Owner:  NLM     Status:  MEDLINE    
Z1046, (S)-6[[6-[[2-(2-methoxyphenoxy)ethyl]amino]propyl]amino]-5,6,7,8-tetra-h ydro-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 microg kg(-1) intravenously or 1 microg 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 microg 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.
A Végh; J G Papp; C Semeraro; Z Fatehi-Hasanabad; J R Parratt
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  344     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1998 Mar 
Date Detail:
Created Date:  1998-07-09     Completed Date:  1998-07-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  203-13     Citation Subset:  IM    
Department of Pharmacology, Albert Szent-Gyorgyi Medical University, Szeged, Hungary.
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MeSH Terms
Blood Pressure / drug effects
Domperidone / pharmacology
Dopamine Agonists / therapeutic use*
Heart Rate / drug effects
Myocardial Ischemia / drug therapy*
Myocardial Reperfusion Injury / drug therapy*
Naphthols / therapeutic use*
Rats, Sprague-Dawley
Splanchnic Circulation / drug effects
Reg. No./Substance:
0/Dopamine Agonists; 0/Naphthols; 0/Z1046; 57808-66-9/Domperidone

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