Excitatory and inhibitory effects of H1-blockers on isolated bullfrog spinal cords

Effects of pyrilamine and diphenhydramine on isolated spinal cords of bullfrogs were studied in order to clarify the mechanisms of depressant and stimulant actions of H1-blockers on the central nervous system. Pyrilamine and diphenhydramine depressed both the DR-VRP and DR-DRP. Pyrilamine and diphenhydramine also suppressed L-glutamate-induced depolarization of the motoneurones, but they did not depress GABA depolarization at the dorsal root terminals. By switching the perfusate to drug-free Ringer solution, depressed amplitudes of DR-VRP were suddenly increased over the control level (rebound phenomenon). The rebound increase of DR-VRP was inhibited by either tetrodotoxin or D-600. These results suggest that the rebound phenomenon may be due to the effect of H1-blockers 1) inhibiting transmitter release participating in presynaptic inhibition and 2) inducing a rapid recovery from the depressed influx of Na+ and Ca2+ into motoneurones.