Local anesthetic activity and acute toxicity of N-substituted 1,2,3,4-tetrahydro-1- and 2-naphthylamines.
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.
D015057:1-Naphthylamine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity; D015081:2-Naphthylamine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity; D000779:Anesthetics, Local; D000818:Animals; D003315:Cornea / Q000187:drug effects; D005260:Female; D007928:Lethal Dose 50; D051379:Mice; D008813:Mice, Inbred ICR; D009281:Naphthalenes / Q000494:pharmacology*; D011817:Rabbits; D012018:Reflex / Q000187:drug effects; D012584:Sciatic Nerve / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology* / Q000633:toxicity
D000779:Anesthetics, Local; D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; D015057:1-Naphthylamine; D015081:2-Naphthylamine