Central cardiovascular effects of CPU-23, a substituted tetrahydroisoquinoline, in rats

Arch Int Pharmacodyn Ther. 1995 Mar-Apr;329(2):245-54.

Abstract

The cardiovascular effects of intracerebroventricular (i.c.v.) injections of low doses of CPU-23, a substituted tetrahydroisoquinoline, were investigated and compared with those of nifedipine in pentobarbital-anaesthetized Sprague-Dawley rats. CPU-23, in doses of 0.2 to 0.5 mg/kg (i.c.v.), which did not elicit any significant cardiovascular responses when injected intravenously, caused a clear-cut and long-lasting decrease of mean arterial pressure (MAP) and heart rate (HR) in a dose-dependent manner. The effects of CPU-23, in a dose of 0.05 mg/kg, were similar to those of nifedipine, a prototype L-type calcium antagonist. The hypotensive effects of CPU-23 were significantly attenuated by bilateral cervical vagotomy. The results strongly suggest that a central component may be involved in the cardiovascular effects of CPU-23 and that dihydropyridine receptor sites in the brain may be involved in the central control of cardiovascular functions.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Blood Pressure / drug effects*
  • Calcium Channel Blockers / administration & dosage
  • Calcium Channel Blockers / pharmacology
  • Calcium Channel Blockers / therapeutic use
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Calcium Channels, L-Type
  • Cardiovascular Agents / administration & dosage
  • Cardiovascular Agents / pharmacology*
  • Cardiovascular Agents / therapeutic use
  • Dose-Response Relationship, Drug
  • Heart Rate / drug effects*
  • Injections, Intraventricular
  • Isoquinolines / administration & dosage
  • Isoquinolines / pharmacology*
  • Isoquinolines / therapeutic use
  • Male
  • Nifedipine / administration & dosage
  • Nifedipine / pharmacology
  • Nifedipine / therapeutic use
  • Piperidines / administration & dosage
  • Piperidines / pharmacology*
  • Piperidines / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cholinergic / drug effects
  • Structure-Activity Relationship
  • Tetrahydroisoquinolines*
  • Vagotomy

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Calcium Channels, L-Type
  • Cardiovascular Agents
  • Isoquinolines
  • Piperidines
  • Receptors, Cholinergic
  • Tetrahydroisoquinolines
  • CPU 23
  • Nifedipine