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

Authors

  • Anthony T. Dren,

    Corresponding author
    1. Department of Pharmacology and Medicinal Chemistry and the Department of Organic Research, Abbott Laboratories, North Chicago, IL 60064
    • Department of Pharmacology and Medicinal Chemistry and the Department of Organic Research, Abbott Laboratories, North Chicago, IL 60064
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  • Barbara A. Bopp,

    1. Department of Pharmacology and Medicinal Chemistry and the Department of Organic Research, Abbott Laboratories, North Chicago, IL 60064
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  • Donn M. Ebert,

    1. Department of Pharmacology and Medicinal Chemistry and the Department of Organic Research, Abbott Laboratories, North Chicago, IL 60064
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  • Adolph O. Geiszler,

    1. Department of Pharmacology and Medicinal Chemistry and the Department of Organic Research, Abbott Laboratories, North Chicago, IL 60064
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  • James B. Holland,

    1. Department of Pharmacology and Medicinal Chemistry and the Department of Organic Research, Abbott Laboratories, North Chicago, IL 60064
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  • Bruce W. Horrom,

    1. Department of Pharmacology and Medicinal Chemistry and the Department of Organic Research, Abbott Laboratories, North Chicago, IL 60064
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  • D. A. Dunnigan

    1. Department of Pharmacology and Medicinal Chemistry and the Department of Organic Research, Abbott Laboratories, North Chicago, IL 60064
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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.

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