Integrative cardiovascular actions of a novel catecholamine, GP-2-128

J Cardiovasc Pharmacol. 1994 Mar;23(3):485-91.

Abstract

Systematic modification in the chemical structure of dobutamine resulted in production of a long-acting, highly potent catecholamine, GP-2-128 [(1-(3,4-dihydroxyphenyl)-2-[3-(4-carbamyl phenyl)-1-methylpropylamino] ethanol)]. The cardiovascular actions of GP-2-128 were compared with those of isoproterenol (ISO) and dobutamine (DOB) in anesthetized dogs. GP-2-128 significantly increased left ventricular pressure (LVdP/dtmax), cardiac output (CO), and heart rate (HR). It also reduced total peripheral vascular resistance (TPVR). For a given increase in contractility, changes in HR were greater after ISO than after GP-2-128 administration. DOB did not change HR significantly. Both GP-2-128 and DOB reduced TPVR, but ISO was more effective than GP-2-128 and DOB in reducing TPVR. GP-2-128 was 18,000 and 52 times more potent than DOB and ISO, respectively, in increasing LVdP/dtmax. For a given increase in contractility, the cardiovascular actions of GP-2-128 lasted significantly longer than those of DOB or ISO. A 50% mixture of the RR and RS distereoisomer forms of GP-2-128 (GP-2-114) have the same pharmacologic profile as the pure RR distereoisomer. Both GP-2-128 and GP-2-114 produced current-dependent cardiovascular actions when administered by transdermal iontophoresis. The inotropic and chronotropic effects of GP-2-128 are both largely due to stimulation of beta-adrenoceptors, as shown by receptor blockade with propranolol. GP-2-128 is a very potent, long-acting catecholamine that can be administered by other than intravenous (i.v.) route.

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Benzamides / administration & dosage
  • Benzamides / pharmacology*
  • Cardiac Output / drug effects
  • Cardiovascular Agents / administration & dosage
  • Cardiovascular Agents / pharmacology*
  • Catecholamines / administration & dosage
  • Catecholamines / pharmacology*
  • Dobutamine / pharmacology
  • Dogs
  • Female
  • Half-Life
  • Heart Rate / drug effects
  • Hemodynamics / drug effects*
  • Injections, Intravenous
  • Iontophoresis
  • Isoproterenol / pharmacology
  • Male
  • Muscle Contraction / drug effects
  • Myocardial Contraction / drug effects
  • Stereoisomerism
  • Vascular Resistance / drug effects

Substances

  • Adrenergic beta-Antagonists
  • Benzamides
  • Cardiovascular Agents
  • Catecholamines
  • 1-(3,4-dihydroxyphenyl)-2-(3-(4-carbamylphenyl)-1-methylpropylamino)ethanol
  • Dobutamine
  • Isoproterenol