G1-0-8 Surface anesthesia on the cornea of rabbits
Transcrição
G1-0-8 Surface anesthesia on the cornea of rabbits
G.1.0.8 Surface anesthesia on the cornea of rabbits PURPOSE AND RATIONALE Following the pioneering work of Sollmann (1918), block of the rabbit corneal reflex as described by Régnier (1923) has become a standard test method for evaluating local anesthetics. PROCEDURE Albino rabbits of either sex weighing 2.5–3 kg are placed into rabbit holding cages. The upper and lower eyelashes are carefully clipped. The conjunctival sac of one eye is held open, thus forming a pocket. From a 1 ml syringe with a 22-gauge needle, 0.5 ml of a solution of the anesthetic is applied into the conjunctival sac for 30 sec. Then the procedure is repeated, so that 1.0 ml is applied within 1 min. One ml of the standard (0.1% solution of tetracaine hydrochloride) is applied to the other eye. Effective local anesthetics extinguish the corneal reflex (blinking) elicited by any touch of the cornea. For quantitative purposes, the irritation with a bristle according to von Frey (1894, 1896, 1922) has been recommended. An equine hair bending at a load of 230 mg is attached perpendicularly to a glass rod. Within 25 sec, the cornea is touched 100 times. The summation of many stimuli applied this way gives better results than a single touch with a glass rod. The test is started 5 min after application of the drug and repeated every 5 min until anesthesia vanishes and blinking occurs again. The time between disappearance and reappearance of the corneal reflex is registered. EVALUATION Using the time of loss of the corneal reflex as parameter after application of different doses, dose-response curves can be established and potency ratios versus the standard calculated. MODIFICATIONS OF THE METHOD Chance and Lobstein (1944) used guinea pigs for testing surface anesthesia by the corneal reflex. REFERENCES Camougis G, Takman BH (1971) Nerve and nerve-muscle preparations (as applied to local anesthetics) In: Schwartz A (ed) Methods in Pharmacology, Vol 1, pp 1–40. Appleton-Century-Crofts, Educational Division, Meredith Corp., New York Chance MRA, Lobstein H (1944) The value of the guinea pig corneal reflex for tests of surface anesthesia. J Pharm Exp Ther 82:203–210 Gerlough TD (1931) The influence of pH on the activity of certain local anesthetics as measured by the rabbit’s cornea method. J Pharmacol Exp Ther 41:307–316 Muschaweck R; Habicht R, Rippel R (1986) Lokalanaesthetica. In: Ehrhart G, Ruschig H (eds) Arzneimittel. Entwicklung – Wirkung – Darstellung. Verlag Chemie GmbH, Weinheim. pp 1–44 Nieschulz O, Hoffmann I, Popendiker K (1958) Zur Pharmakologie des N-[4-(Phenoxy-methyl)-γ-phenyl-propyl]-morpholin, eines Aminoäthers mit lokalanaesthetischer Wirkung. Arzneim Forsch 8:539–544 Régnier MJ (1923) Essai de mesure de l’anesthésie produite sur les terminaisons nerveuses de la cornée par les anesthésiques locaux. Comparaison des pouvoirs anesthésiques de la cocaïne, de la novocaïne et de la stovaïne. C R hebd Scéances Acad Sci 177:558–560 Sollmann T (1918) Comparison of activity of local anesthetics. IV. Anesthesia of rabbit’s cornea. J Pharmacol Exp Ther 11:17–25 Štolc S, Mai PM (1993) Comparison of local anesthetic activity of pentacaine (trapencaine) and some of its derivatives by three different techniques. Pharmazie 48:210–212 Ther L (1953 a) Zur Prüfung der lokalanästhetischen Wirkung des Pantocain und des 4-n-Butylaminosalicylsäuredimethylaminoaethylesters im Tierversuch. Arzneim Forsch 3: 345–348 Ther L (1953 b) Über ein neues Leitungsanaesthetikum der “Nirvanin”-Reihe mit großer Entgiftungsgeschwindigkeit (Hostacain). Naunyn Schmiedeberg’s Arch exper Path Pharmakol 220:300–316 von Frey M (1894) Beiträge zur Physiologie des Schmerzsinns. Ber Sächs Gesellsch Wiss, Leipzig, Math Phys Kl 46:185–195 von Frey M (1896) Untersuchungen über die Sinnesfunctionen der menschlichen Haut. Erste Abhandlung: Druckempfindung und Schmerz. Abhandl. der Mathematisch-physikalischen Classe d. Königl. Sächs. Gesellsch. der Wissensch. 23:173–266. von Frey M (1922) Versuche über schmerzerzeugende Reize. Z Biologie 76:1–24 Wiedling S (1960) Studies on α-n-propylamino-2-methylpropionanilide – a new local anaesthetic. Acta Pharmacol Toxicol 17:233–244