Effects of dopamine and selective dopamine agonists upon platelet accumulation in the cerebral and pulmonary vasculature of the rabbit.
1. A selection of novel compounds were shown to exhibit dopaminergic activity in vitro. 2. 111Indium-labelled platelets were continuously monitored in the cerebral and pulmonary vasculature of anaesthetized rabbits. The effects of dopamine and selective dopamine receptor agonists on ADP and thrombin induced platelet accumulation were recorded. 3. Pretreatment with dopamine (2 mg kg(-1) min(-1), i.v.) significantly reduced ADP (20 microg kg(-1), i.v.) induced platelet accumulation in the pulmonary vasculature whereas lower doses had no effect. 4. Dopamine (100 microg kg(-1) min(-1) intra-carotid, i.c.) potentiated thrombin (90 u kg(-1), i.c.) induced platelet accumulation in the cerebral vasculature whereas higher doses (1-2 mg kg(-1) min[-1]) inhibited accumulation. 5. The selective dopamine receptor agonists tested did not significantly inhibit platelet accumulation induced by ADP or thrombin. Two of these selective agonists, at doses higher than the intended therapeutic doses, induced thrombocytopaenia and an associated increase in platelet accumulation in the lung in response to thrombin. 6. These results extend previous in vitro studies regarding the dual actions of dopamine upon platelets and show for the first time the effects of selective dopamine receptor agonists upon platelet aggregation in vivo.
Emerson
M
M
Sackler Institute of Pulmonary Pharmacology, King's College London.
Paul
W
W
Ferlenga
P
P
Semeraro
C
C
Page
C
C
D015081:2-Naphthylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects*; D001921:Brain / Q000098:blood supply*; D004298:Dopamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007205:Indium Radioisotopes; D008168:Lung / Q000098:blood supply*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D013844:Thiazoles / Q000494:pharmacology
D018491:Dopamine Agonists; D007205:Indium Radioisotopes; C109444:N-propyl-N-(6-(2-(2-oxo-3H-1,3-benzothiazol-6-yl)ethylamino)hexyl)-5,6-dihydroxy-1,2,3,4-tetrahydro-2-naphthylamine dihydrobromide; C109445:N-propyl-N-(6-(2-(3,5-dihydroxyphenyl)ethylamino)hexyl)-5,6-dihydroxy-1,2,3,4-tetrahydro-2-naphthylamine; D013844:Thiazoles; D015081:2-Naphthylamine; D004298:Dopamine