Inotropic and chronotropic effects of 4-(4'-n-butylaniline)-7,8- dimethoxy-5H-pyrimido[5,4-b]indole in guinea-pig atria

J Pharm Pharmacol. 1995 Jul;47(7):601-7. doi: 10.1111/j.2042-7158.1995.tb06722.x.

Abstract

Cardiotonic effect of 4-(4'-n-butylaniline)-7,8-dimethoxy- 5H-pyrimido[5,4-b]indole (B11) was investigated in isolated cardiac tissue preparations. The action of this agent on force of contraction, beating frequency and cyclic nucleotide phosphodiesterase (PDE) activity was studied. Amrinone was used for comparison. B11 produced concentration-dependent (5 x 10(6)-1 x 10(-4)M) positive inotropic and positive chronotropic responses in guinea-pig atrial tissues. The potency of B11 was greater than that of amrinone. The cardiotonic effects of B11 were not modified by beta-adrenoceptor blockade. Carbachol inhibited the positive inotropic effect of B11. The activity of B11 was increased in desensitized left atrial tissues. B11 inhibited the activities of PDE isoenzymes (type I, II, IV and V) from dog heart ventricle and PDE type IV from guinea-pig heart ventricle nonselectively. It is concluded that B11 possesses potent positive inotropic activity in guinea-pig atria, and the effect is probably mediated by a non-selective inhibition of PDE activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / drug effects
  • Adrenergic beta-Antagonists / pharmacology
  • Amrinone / pharmacology
  • Animals
  • Carbachol / pharmacology
  • Cardiotonic Agents / pharmacology*
  • Cyclic AMP / metabolism
  • Cyclic GMP / metabolism
  • Dogs
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Heart / drug effects*
  • Heart Atria / drug effects
  • Heart Ventricles / drug effects
  • Heart Ventricles / enzymology
  • Indoles / administration & dosage
  • Indoles / pharmacology*
  • Isoenzymes
  • Isoproterenol / pharmacology
  • Male
  • Myocardial Contraction / drug effects*
  • Phosphodiesterase Inhibitors / pharmacology*
  • Pyrimidines / administration & dosage
  • Pyrimidines / pharmacology*

Substances

  • 4'(4'-n-butylanilino)-7,8-dimethoxy-5H-pyrimido(5,4-b)indole
  • Adrenergic beta-Antagonists
  • Cardiotonic Agents
  • Indoles
  • Isoenzymes
  • Phosphodiesterase Inhibitors
  • Pyrimidines
  • Carbachol
  • Cyclic AMP
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic GMP
  • Amrinone
  • Isoproterenol