The effects on the central nervous system as well as other actions of syrosingopine were studied and compared with those of reserpine and rescinnamine. These rauwolfia alkaloids exhibited inhibitory effects on gross behavior, locomotor activities and conditioned avoidance response, and elicited cataleptic, muscle relaxant and gastric ulcerating effects. The alkaloids revealed a drowsy pattern in the spontaneous EEG activity and depressed the EEG arousal response. In those central actions, reserpine was the best, rescinnamine next and syrosingopine least, in that diminishing order of potency. Syrosingopine prolonged the hypnotic effect of thiopental sodium and this action was weaker than that of reserpine. Reserpine inhibited the analgesic effect of morphine, while syrosingopine did not. Syrosingopine excited slightly the movement of intestine but did not influence movement of the uterus. The stellate ganglionic transmission was slightly inhibited but the electrocardiogram was not influenced by syrosingopine. These alkaloids had similar potency in the depressor and negative chronotropic effect, although they showed a different potency in their central actions.
Pharmacological properties of L-5HTP in experimental animals were studied and the following results were obtained: L-5HTP produced a decrease in spontaneous locomotor activity in mice, a potentiation of morphine-induced analgesia in mice, an effect of lowering body temp. in mice and a tendency to induce a drowsy EEG pattern in rabbits. Anticonvulsant, anti-tremor, muscle relaxant effects and a potentiation of pentobarbital-induced aneasthesia were not induced by L-5HTP. On the other hand, L-5HTP antagonized the behavioral changes induced by reserpine, tetrabenazine and p-CPA in some experiments.
In the rat seminal vesicle, sensitivity to norepinephrine, epinephrine, acetylcholine and tyramine was increased by castration and the contractile responses showed a spontaneous phasic contraction. The sensitivity was markedly increased by estradiol treatment after castration and decreased by testosterone treatment. In the vas deferens, the contractile response to acetylcholine was weaker than that of norepinephrine, while in the 30 day castrated group it increased only the sensitivity to acetylcholine and testosterone treatment depressed only the sensitivity. Rhythmic contraction was observed on the vas deferens in the 30 day castrated rats. Testosterone treatment inhibited rhythmic response. In the 35_??_40 day castrated rats, spontaneous rhythmic contraction was also observed in the vas deferens. The frequency of the contraction was increased by application of high-K+ 10_??_40mM, and was decreased by high-Ca++ 1_??_10mM, however, the contractile response was increased. The spontaneous rhythmic contraction was not affected with TTX, atropine, cocaine, procaine, propranolol and reserpinization, however, a high dose of guanethidine, phentolamine depressed the contraction. From these observations, it is considered that the motility of the vas deferens and the seminal vesicle is controlled by gonadal hormones, and that androgen especially, exerts an inhibitory action on the motility of the genital musculature of the male rats while castration increases the sensitivity of the postsynaptic membrane.
It has been shown that 1-[2-(dodecyloxy) ethyi] pyrrolidine hydrochloride (DEP) has a strong wormcidal action on Ascaris lumbricoides suum. In this paper, absorption pathways into Ascaris body and the mechanism of wormcidal action were investigated with the following results. It was confirmed that DEP was mainly absorbed from the cuticle of Ascaris body in the form of non-ionic base. DEP (100μg/ml) caused a sustained contraction of Ascaris muscle preparation. This contraction was not blocked by d-tubocurarine or other cholinolytics. DEP caused contraction of Ascaris muscle preparation previously depolarized with high K+ solutions or treated with triton X-100. When Ascaris muscle preparation was immersed in a Ca-free solution containing EGTA 2mM for 2hr, DEP did not induce a contraction. DEP did not cause a contraction of the glycerol muscle of Ascaris. These results suggest that DEP induces a contraction triggered by releasing calcium from the sarcoplasmic reticulum.
Pharmacological properties of the surugatoxin from Japanese ivory shell (Babylonia japonica) (Kosuge et al. 1972, Gohgi et al. 1973) were studied, and its properties were compared with those of IS-toxin (Hirayama et al. 1970, 1972, Gohgi et al. 1973) isolated from the same shell. Surugatoxin (0.15_??_0.2mg/kg i. v.) reduced spontaneous movement, causing a drowsiness, mydriasis and relaxation of nictitating membrane in cats. The toxin had no effects either on the neuromuscular junctions or on the striated and smooth muscles. Contractile responses of the guinea-pig ileum preparations to nicotine (1×10-7g/ml) were observed, and the responses to nicotine were abolished by hexamethonium (C6, 4×10-4g/ml). Surugatoxin, on the other hand, at a concentration of 1×10-7_??_1×10-6g/ml reduced or eliminated the responses to nicotine and to 1, 1-dimethyl-4-phenylpiperazium iodide (DMPP, 1×10-6g/ml), but the contractile responses due to 4-(m-chlorophenyl-carbomyloxy)-2-butynyltrimethylammonium chloride (McN-A-343, 1×10-5g/ml) were scarcely effected by the toxin at the same concentrations. The toxin was assumed to have a ganglionic blocking action in the inner plexus of the intestine. Accordingly, effect of the toxin on the superior cervical sympathetic ganglion of cats was studied using the Trendelenburg method (1954, 1956). Surugatoxin injected into the femoral vein (150_??_200μg/kg) or the lingual artery (40_??_50μg/kg, to the ganglion) decreased or abolished the contractile responses of the nictitating membrane and the post-ganglionic external potentials to an electrical stimulation of the pre-ganglionic nerve. Surugatoxin did not however, alter responses to the post-ganglionic nerve stimulation. Injection of surugatoxin (40_??_50μg/kg, to the ganglion) reduced or eliminated contractions of the nictitating membrane due to 2μg/kg of DMPP (to the ganglion), a nicotinic ganglionic stimulant (Chen et al. 1951, 1953) and to 25μg/kg of candicine, a ganglionic stimulant (Urakawa et al. 1959, Deguchi et al. 1963), while the contractions due to 2.5_??_5μg/kg of McN-A-343 (to the ganglion), a muscarinic stimulant (Raszkowski, 1961) were scarcely effected by the toxin with the same dose. When 40_??_50μg/kg of surugatoxin was administered (to the nictitating membrane), it affected neither the responses of nictitating membrane nor the pressor responses of systemic blood pressure induced by norepinephrine (5μg/kg, to the nictitating membrane). The potency of surugatoxin, determined in a manner similar to that described by Gyermek (1957) was about 6 times as strong as that of hexamethonium. It is suggested, that the mode of ganglioplegic action of the surugatoxin is similar to that of IS-toxin (Hirayama et al. 1972), which may be due to an inhibitory action on the nicotinic ganglionic receptors in the inner plexus of the intestine and in the superior cervical nerve. Surugatoxin may be a specific inhibitor on the nicotinic ganglionic receptors in autonomic ganglia.
Effects of certain hypnotic agents on the sleep and wakefulness cycle in the rabbit with chronically implanted electrodes were studied. The onset of paradoxical sleep (PS) episode was delayed progressively with increasing doses of pentobarbital and bromoisovalerylurea. During PS episodes at the early periods after these drugs, the frequency of hippocampal theta activity was reduced and the desynchronization of corticogram was obscure. In many cases, phasic activity including rapid eye movement (REM), and twitching of the muscles of the face and extremities were absent. Following administration of thalidomide, spindle sleep (SS) was markedly increased, but PS was only slightly affected and polygraphic aspects during SS and PS were almost the same as those of control recordings. It is suggested that the physiological sleep like state was induced by this drug.
During paradoxical sleep (PS), distinct spike waves resembling ponto-geniculo-occipital (PGO) activity in the cat were recorded in the medial or ventral nucleus Trapezoides in the rabbit, using chronically implanted electrodes. These spike waves were 25_??_100μV in amplitude, 30_??_80 msec in duration, and often grouped in a burst of 5_??_20 waves. In many cases, these spike waves preceded the appearance of hippocampal theta activity at the beginning of the PS episodes by several seconds. Almost the same spike waves as PS episodes were continuously observed after reserpine administration. Except for a few cases, these spike waves resembled PGO activity in the genesis. Following administration of pentobarbital or bromoisovalerylurea, the spike waves appeared periodically even when the slow waves were prominent in the motor cortex and hippocampus. This phenomenon suggests that the triggering mechanism of PS works periodically when the appearance of PS episodes are suppressed by hypnotic agents.