2-trimethylaminoethyl-1'-ethylisothiuronium bromide hydrobromide (ETMA) produced a marked fall in the blood pressure of anesthetized cats. This action was not antagonized by atropine. Pressor response to adrenaline in cats and inhibitory response to electrical stimuli in Finkleman preparation of isolated rabbit jejunum were not blocked. ETMA, however, blocked blood pressure response to nicotine, to occlusion of the carotid arteries and to stimulation of the cardiac end of the cut right vagus. The contraction of the nictitating membrane in cats produced by stimulation of the preganglionic fiber, administration of DMPP (i. a.) and MTMA (i. a.) was blocked by intra-arterial injection of ETMA. The response to stimulation of the postganglionic fiber, adrenaline (i. a.) and KCl (i. a.) was not affected. These results suggest that the ETMA-induced hypotension could be related to blockade of the autonomic ganglia, presumably acting on the ganglion cell at the postsynaptic cholinoceptive site.
Distribution of 3H-nicotine in 26 tissues of rhesus monkeys and dogs was studied following intravenous injection of 10, 100 and 500μg/kg of the drug. (1) It was confirmed in both species that within 5min. after injection the highest concentration of 3H-nicotine was observed in target organs such as central nervous system and adrenal gland. (2) High concentration of 3H-radioactivity 30min. after injection was found in the kidney, salivary gland, stomach and intestinal mucosa. These results suggest that excretion of nicotine from these organs begins soon after injection. (3) Distribution of 3H-nicotine in skeletal muscles and fatty tissues of monkeys was higher than those of dogs. This results in that distribution in central nervous system and serum of monkeys was lower than those of dogs. These differences may elucidate the factors of nicotine sensitivity among the species.
Functional properties of thalamic relay cells in VPM and PO activated by electrical stimulation of tooth pulp, and effect of morphine on these cells were investigated electrophysiologically in rats. 1) Unitary responses evoked by electrical stimulation of tooth pulp were recorded from VPM and PO cells. 2) Functional properties of VPM cells differed from those of PO cells in regard to receptive field, latency, spike number and threshold. Cells belonging to VPM generally responded to specific peripheral field, but not so with those belonging to PO. Latency distribution of the first spikes in VPM gathered at 5, 10, 15 msec and that in PO extended over 5 to 25 cosec. In bilaterally responsive cells, latencies after the stimulation of contralateral tooth pulp (CTP) were shorter than those after the stimulation of ipsilateral tooth pulp (ITP) both in VPM and PO. Number of the spikes evoked by the stimulation of pulp was usually single in VPM, but numerous in PO. Intensity of stimulation in VPM showing the maximal spike number was greater than that in VPM. 3) Forty percent of VPM cells and 80 percent of PO cells were depressed by morphine (10mg/kg). This depression, though antagonized by levallorphan (0.1mg/kg), was recognized as a reduction of spike number and a prolongation of latency. 4) Morphine (20mg/kg) did not depressed the spikes in VPM evoked by tactile stimulation, however those in PO evoked by pin pricking were depressed by 5_??_10mg/kg.
It is evident from past experience that tooth extraction increases stress in animals. The author investigated the change in the amount of adrenal corticosterone at the time of extraction and also how dietary protein is utilized herein. Results are as follows: 1. Weight of adrenal glands of the low protein diet rat group is considerably less than that of normal. 2. Low protein cage fed diet group take longer time to recover from increased adrenal corticosterone than a normal group. 3. Weight of adrenal glands of the low protein diet group increased under extraction stress whereas no effect was observed in the case of a normal protein group. 4. Low protein diet group took longer to recover from abnormal amount of adrenal corticosterone resulting from extraction stress.
Cardiovacular actions of Salbutamol in dogs were compared with those of Isoproterenol. Both drugs exhibited positive inotropic, chronotropic and peripheral vasodilating effects due to β-adrenergic stimulation. Vasodilating effect of Salbutamol was 10 to 30 times less potent as that of Isoproterenol, while cardiac effect of the former was approx. 30 to 60 times less potent than that of the latter. Qualitative differences were also suggested between cardiovascular actions of Salbutamol and Isoproterenol; i.e., (1) Positive inotropic action of Salbutamol was not potentiated even in the failing heart. (2) Salbutamol exerted no α-adrenergic stimulating action.
1) Subcutaneous administration of CG-315 to rats was followed by rapid absorption and distribution, especially highly in lung, spleen, liver, and kidney etc. Most of the injected drug was excreted in the urine within 24 hrs and a few in the feces. 2) Part of absorbed CG-315 may be mainly metabolized in liver to either O- or N-demethylated forms, some of which are conjugated with glucuronate. 3) No difference was found in metabolism of CG-315 between non-tolerant and tolerant rats.
Pharmacological properties of a new analgesic drug K-315 were investigated in dogs, cats, rabbits, guinea-pigs, rats and mice. Results obtained are as follow: Analgesic action of K-315 antagonized by levallorphan was less than those of morphine and pethidine, but similarly potent to that of dihydrocodeine. K-315 also potentiated responses of adrenaline to nictitating membrane and cardiovascular organs in dogs, cats and rabbits, , while pethidine revealed inhibition. K-315 obviously had the anti-tussive effects in cats and guinea-pigs.
Effects of a new analgesic drug, K-315, on the central nervous system were investigated electro-encephalographically and neurophpsiologically. Results are as follows: 1. K-315 slightly synchronized spontaneous EEG, and inhibitory actions of arousal responses following stimulation of subcortical areas were less than those of pethidine. 2. K-315 slightly potentiated recruiting and augmenting responses in rabbits, but did not affect the induced spindle burst. 3. K-315 strongly inhibited cortical responses evoked by splanchnic nerves stimulation in the equivalent dose of morphine in cats. 4. K-315 showed differential actions from that of morphine in cortical responses evoked by CM stimulation.