THE LOCAL ANAESTHETIC ACTIONS OF CERTAIN PYRAZOLINE AND QUINOLINE COMPOUNDS

¹ From the Department of Pharmacology, University of Edinburgh

1. The rate of paralysis of the frog's sciatic by local anaesthetics is very variable and in order to obtain reliable comparative results it is necessary to obtain averages from a large number of experiments.

2. The rate of onset of anaesthesia in the rabbit's cornea is unsuitable as a measure of local anaesthetic potency because the curves relating concentrations and rates of actions of different drugs often cross, so that different ratios of activity are obtained with every concentration that is studied.

3. The duration of action produced by local anaesthetics on the rabbit's cornea and on the human wheal are possible methods for quantitative measurements.

4. The cornea of different rabbits show considerable individual variation but this can be eliminated by making repeated experiments on a single rabbit.

5. There is an approximate linear relation between the logarithm of the concentration of a local anaesthetic and the duration of action produced on both the rabbit's cornea and the human wheal.

6. Since there is no simple linear relation between time and concentration it is not possible to estimate differences in local anaesthetic potency by measuring differences as the duration of action. The fact that drug A produces an action of twice the duration of that produced by drug B at the same concentration does not imply that A is twice as potent as B.

7. The simplest method for comparing the relative potency of local anaesthetics is to measure the concentrations which produce local anaesthesia for some standard time. This method can be employed either with the rabbit's cornea or with the wheal method. The addition of adrenaline to local anaesthetics may change the ratio of activity as determined by the wheal method.

8. Of the three compounds tested the pyrazoline derivative (XVI/8) and the diquinoline derivative (XVII) may be of value for clinical application to mucosae and for infiltration anaesthesia. The quinoline derivative (XVIII/1) is just equal to novocaine in nerve trunk anaesthesia.