Effects of S14001 on adrenergic neuroeffector interaction in isolated canine saphenous veins

Gen Pharmacol. 1992 Sep;23(5):867-72. doi: 10.1016/0306-3623(92)90239-g.

Abstract

1. The effects of (S) fluoro-6 (morpholinyl-2 methoxy)-8-tetrahydro-1,2,3,4 quinoleine (S14001) on adrenergic neurotransmission in isolated canine saphenous veins were investigated in experiments which measured the accumulation, overflow and metabolism of 3H-norepinephrine. 2. S14001 inhibited the accumulation of total tritium (3H-norepinephrine and 3H-metabolites of norepinephrine) in a concentration-dependent manner. 3. Under basal conditions, S14001 increased tension and basal effiux of total tritium; the latter consisted predominantly of 3H-DOPEG. The increases in these parameters were not inhibited by desmethylimipramine (DMI). 4. During electrical stimulation, S14001 increased the contraction and overflow of total tritium; the latter consisted predominantly of 3H-DOPEG. The increases in these parameters were inhibited by DMI. 5. These experiments suggest that S14001 has dual effects on adrenergic neurotransmission in the canine saphenous vein: (a) an inhibitory action on the neuronal accumulation; and (b) a pharmacological displacement of the transmitter from adrenergic nerve terminals.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Desipramine / pharmacology
  • Dogs
  • Electric Stimulation
  • Isometric Contraction / drug effects
  • Morpholines / pharmacology*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / innervation
  • Neuroeffector Junction / drug effects*
  • Neuroeffector Junction / physiology
  • Norepinephrine / metabolism
  • Quinolines / pharmacology*
  • Receptors, Adrenergic / drug effects
  • Receptors, Adrenergic / physiology
  • Saphenous Vein

Substances

  • Antidepressive Agents
  • Morpholines
  • Quinolines
  • Receptors, Adrenergic
  • S 14001
  • Desipramine
  • Norepinephrine