title: Modification of cardiovascular actions of 2-amino-5,6-dihydroxytetralin by N,N-di-n-propyl substitution.
abstract: Effects of dopamine (DA) and the N,N-di-n-propyl derivative of 2-amino-5,6-dihydroxytetralin (dipropyl-A-5,6-DTN) were compared on renal blood flow in phenoxybenzamine pretreated dogs. Equivalent increments in renal blood flow were observed in the dose range of 12-190 nmol (ED50 of DA, 1.4 x 10(-8) mol; ED50 of dipropyl-A-5,6-DTN, 1.2 x 10(-8) mol, n = 7). Effects of 47 nmol of DA and dipropyl-A-5,6-DTN were reduced equally by simultaneous injections of 0.5 mg sulpiride (76 +/- 4 and 59 +/- 6%, respectively, n = 5). Intravenous injections of dipropyl-A-5,6-DTN in doses of 4-16 micrograms/kg elevated arterial blood pressure and decreased heart rate and cardiac contractility in open chest, vagotomized dogs, confirming its neuronal inhibitory effect mediated by DA2-presynaptic receptors. Dipropyl-A-5,6-DTN also caused dose-related femoral artery vasoconstriction in the hexamethonium pretreated dog. The hypertensive effect of intravenous dipropyl-A-5,6-DTN and its femoral vasoconstrictor effect were abolished by phenoxybenzamine. These results show that dipropyl-A-5,6-DTN possesses DA1-, DA2- and alpha-adrenergic activities. It is significant that by introducing di-n-propyl substitution on the nitrogen of 5,6-dihydroxy-2-aminotetralin, potent DA1-agonist activity can be conferred upon a molecule which is inactive in that respect. Further, beta-adrenergic activity of the primary amine is replaced by potent alpha-adrenergic activity by this substitution.
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004285:Dogs; D004298:Dopamine / Q000494:pharmacology; D005263:Femoral Artery / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D013329:Structure-Activity Relationship; D013469:Sulpiride / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
chemical_list: D000316:Adrenergic alpha-Agonists; D002317:Cardiovascular Agents; D009281:Naphthalenes; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; C015842:2-(N,N-dipropyl)amino-5,6-dihydroxytetralin; D013469:Sulpiride; D004298:Dopamine