Pharmacological studies of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone(M73101)

(5) Action of M73101 on the central nervous system

Abstract

M73101 decreased spontaneous locomotor activity in both mice and rats and prolonged sleeping time induced by hexobarbital in mice. There was no evidence of cataleptogenic action, anti-tremorine action and antagonistic effect on reserpine-induced hypothermia in mice. M73101 did not inhibit convulsions induced by maximal electroshock and pentylenetetrazol but slightly inhibited the convulsion induced by strychnine in mice. Moreover, M73101 depressed only the monosynaptic action potential in intact and spinal cats, indicating that this compound exerts an inhibitory action on spinal function. On the EEG of rabbits, M73101 produced an arousal pattern in the spontaneous EEG and inhibited the recruiting response, but had no marked influence on the EEG arousal response, augmenting response and hippocampal afterdischarge. The arousal pattern in the spontaneous EEG induced by M73101 and the inhibitory action of this compound on the recruiting response were absent in the cerveau isolé preparation of the rabbit, indicating that M73101 may stimulate the brainstem reticular formation and that the inhibition of recruiting response may be related to the stimulatory effect. These properties of M73101 on the central nervous system are similar to those seen with aminopyrine though the potency was weaker. M73101 like aminopyrine showed no marked activity on the motor function.