Non-specific actions of the non-peptide tachykinin receptor antagonists, CP-96,345, RP 67580 and SR 48968, on neurotransmission

Br J Pharmacol. 1994 Jan;111(1):179-84. doi: 10.1111/j.1476-5381.1994.tb14041.x.

Abstract

1. Three non-peptide tachykinin receptor antagonists, CP-96,345, RP 67580 and SR 48968, were found to inhibit the electrically-evoked, tachykinin-mediated contractile responses of the rabbit iris sphincter in a concentration-dependent fashion; the pIC50 values were 5.6 +/- 0.01, 5.4 +/- 0.07 and 4.8 +/- 0.03, respectively. 2. These antagonists also inhibited the electrically-evoked, parasympathetic response of the rabbit iris sphincter and the sympathetic response of the guinea-pig vas deferens in a concentration-dependent manner; the pIC50 values were 0.3-1.2 log units lower than those recorded for the tachykinin-mediated responses. 3. Two local anaesthetics, bupivacaine and oxybuprocaine, were also found to inhibit the tachykinin-mediated, cholinergic and sympathetic contractile responses in these tissues in a concentration-dependent manner; the concentration ranges for producing the inhibition were similar to those of the non-peptide tachykinin receptor antagonists. 4. On the sciatic nerves of frogs, the tachykinin receptor antagonists inhibited action potentials in a concentration-dependent manner; the potency of the three drugs was similar to that of bupivacaine. 5. Our results suggest that, in addition to blocking tachykinin receptors, the non-peptide tachykinin receptor antagonists, CP-96,345, RP 67580 and SR 48968, may exert non-specific inhibitory effects on neurotransmission.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Anesthetics, Local / pharmacology
  • Animals
  • Benzamides / pharmacology*
  • Biphenyl Compounds / pharmacology*
  • Bupivacaine / pharmacology
  • Electric Stimulation
  • Female
  • Guinea Pigs
  • In Vitro Techniques
  • Indoles / pharmacology*
  • Iris / drug effects
  • Isoindoles
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects*
  • Piperidines / pharmacology*
  • Procaine / analogs & derivatives
  • Procaine / pharmacology
  • Rabbits
  • Rana catesbeiana
  • Receptors, Tachykinin / antagonists & inhibitors*
  • Sciatic Nerve / drug effects
  • Synaptic Transmission / drug effects*
  • Vas Deferens / drug effects

Substances

  • Anesthetics, Local
  • Benzamides
  • Biphenyl Compounds
  • Indoles
  • Isoindoles
  • Piperidines
  • Receptors, Tachykinin
  • 7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one
  • Procaine
  • SR 48968
  • benoxinate
  • CP 96345
  • Bupivacaine