Local anesthetic activity and acute toxicity of N-substituted 1,2,3,4-tetrahydro-1- and 2-naphthylamines

J Pharm Sci. 1978 Jun;67(6):880-2. doi: 10.1002/jps.2600670647.

Abstract

Seven N-substituted 1,2,3,4-tetrahydro-1- and three 2-naphthylamines were prepared and tested for local anesthetic activity in the rabbit corneal reflex test and the mouse sciatic nerve block test. At 0.1 and 1%, three 1-alkylamino compounds had durations of action comparable to that of tetracaine in the rabbit corneal reflex test and were considerably more potent than lidocaine. The other four 1-alkylamino derivatives were inactive or at best minimally active. The durations of action of 1% concentrations of the three 2-alkylamino compounds were equivalent to that of 1% lidocaine in the corneal reflex test. In the mouse sciatic nerve block test, the three active 1-alkylamino compounds were considerably longer acting than either tetracaine or lidocaine. Three 1-alkylamino and the three 2-alkylamino compounds showed toxicity equal to or greater than lidocaine, while two 1-alkylamino and two 2-alkylamino compounds showed toxicity equal to or greater than tetracaine by the intraperitoneal route in mice. N-Heptyl-1,2,3,4-tetrahydro-6-methoxy-1-naphthylamine methanesulfonate was the most promising local anesthetic in these series.

MeSH terms

  • 1-Naphthylamine / analogs & derivatives
  • 1-Naphthylamine / pharmacology
  • 1-Naphthylamine / toxicity
  • 2-Naphthylamine / analogs & derivatives
  • 2-Naphthylamine / pharmacology
  • 2-Naphthylamine / toxicity
  • Anesthetics, Local*
  • Animals
  • Cornea / drug effects
  • Female
  • Lethal Dose 50
  • Mice
  • Mice, Inbred ICR
  • Naphthalenes / pharmacology*
  • Rabbits
  • Reflex / drug effects
  • Sciatic Nerve / drug effects
  • Tetrahydronaphthalenes / pharmacology*
  • Tetrahydronaphthalenes / toxicity

Substances

  • Anesthetics, Local
  • Naphthalenes
  • Tetrahydronaphthalenes
  • 1-Naphthylamine
  • 2-Naphthylamine