Effect of Mephenesin and Other ‘Depressants’ on Spinal Cord Transmission in Frog and Cat

Abstract

The CNS-depressant actions of certain drugs including mephenesin, glyketal, dihydro-beta-erythroidin, cocaine hydrochloride, o-cresol, and P-1, P-2, P-3, and P-4 (P-105) were tested in the frog and the cat. P-4, glyketal, o-cresol and mephenesin in that order were the most potent CNS depressant drugs in frog screening tests, cocaine, P-I, and P-3 were toxic. Ether, P-4, glyketal, prendiol and mephenesin blocked CNS transmission in the cat, the effect being a selective one. The multisynaptic chain was much more vulnerable to the effects of these agents than the monosynaptic path. Erythroidin also blocked CNS transmission but in concentrations well above peripheral paralysis doses, and had no selective action. Analysis of the data shows that an approximately linear relationship exists between drug potency and the number of links in the multineuron chain affected and this relationship can be expressed mathematically by the probability equation P = p-(1-p)n, where p is the probability of any one synapse being blocked and its values vary from 0 to 1 and n is the number of synapses in the pathway. The % change expressed in decimals, i.e., 50% = 0.5, of the monosynapse voltage may be used as a value for p and then the calculated changes (P) of the multisynapse pathways agree well with the observed changes. The blocking action of the drugs is achieved by a lowering of the synaptic potential, similar to the reduction of the endplate potential by curare and in high concentrations the excitability of peripheral nerve and muscle tissue is markedly reduced by these agents.