NICOTINOLYTIC DRUGS. I. DRUGS INHIBITING NICOTINE-INDUCED TREMORS

¹ Maltbie Laboratories, Morristown, N. J.

1. The test of Longo and Bovet can be used for the quantitative evaluation of the activity of nicotinolytic agents. A linear relationship exists between the probit of unanesthetized rabbits protected against nicotine tremors and the logarithm of the dose of the antagonist. The average dose protecting 50 per cent of the animals can be evaluated graphically.

2. A group of compounds different chemically and pharmacologically seem to have the common feature of blocking or interfering with nicotine-induced tremors:

a. Drugs clinically active against the Parkinson syndrome show clear-cut antagonism to tremors produced by nicotine. The average protective doses, expressed in mgm./kgm., are: Diparcol 3.7, Panparnit 1.8, Artane 3.3, and Trasentine 1.2.

b. Neuromuscular blocking agents exhibit a striking inhibition of nicotine tremors. The average effective doses, expressed in mgm./kgm., are: d-tubo- curarine 0.15, decamethonium bromide 0.11, Lucaine 1.9, procaine 6.2, diacetylcholine 0.6.

c. Central depressants protect 50 per cent of the rabbits at the following doses: Dilantin 16 mgm./kgm., Phenobarbital 29 mgm./kgm., Pentobarbital 2.2 mgm./kgm.

d. An interneuronal depressant, mephenesin, shows an average protection at 25 mgm./kgm.

3. Various compounds are ineffective against nicotine tremors unless toxic effects or side effects are observed.

a. Parasympatholytic drugs protect against nicotine tremors only at toxic levels: 40 mgm./kgm. for atropine (ED₃₃) and 49 mgm./kgm. for scopolamine (ED₅₀).

b. Ganglionic blocking agents are effective against nicotine tremors only in doses which cause neuromuscular block, such as 4.8 mgm./kgm. for Banthine, 20 mgm./kgm. for pentamethonium bromide, 16 mgm./kgm. for hexamethonium bromide. Tetraethylammonium bromide is active in 33 per cent of rabbits only at 75 mgm./kgm.; toxic symptoms occur at that dose.

4. The block of nicotine tremors in the rabbit is a valuable test for the screening of anti-Parkinson drugs; it is not, however, specific.

After completion of this manuscript the recent paper of D. Bovet and V. Longo (This Journal, 102: 22, 1951) was brought to our attention.