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The classical view of the neuromuscular transmission is that non-depolarizing muscle relaxants (MRs) enhance run-down of the endplate potentials (epps) by blocking pre-junctional nicotinic acetylcholine (ACh) receptors. Several recent investigations, when extended to pharmacology, have provided evidence to suggest the existence of other types of enhancement of run-down of epps by MRs; the enhancement of epps occurs without reduction of ACh release in the presence of MRs. It has been generally accepted that the enhancement of run-down of epps causes the tetanic fade of tension response. However, recent evidence indicates that run-down of epps does not always cause this wane in tension. The electrophysiological mechanism of run-down of epps at the neuromuscular junction and the relationship between that phenomenon and the extent of reduction of tension response are described based on a review of literature and our current investigations.

Propiverine hydrochloride (P-4) is a new derivative of benzilic acid. The effect of P-4 on the vesico-detrusor reflex (corresponding to the first reflex of Barrington) in anesthetized or decerebrated dogs was studied to elucidate the mode of action of the drug. When bladder contraction was induced by electrical stimulation of the distal ending of the pelvic nerve under the bilateral pelvic nerve and hypogastric nerve transection, P-4 (2, 5 and 10 mg/kg, i.v.) significantly inhibited the contraction. A similar effect was also observed following intravenous administration of flavoxate (10 and 20 mg/kg), verapamil (1 mg/kg) or propantheline (2 mg/kg), while thiopental (4 mg/kg, i.v.) had no significant effect. When the bladder was filled under the bilateral pelvic nerve and hypogastric nerve transection, an increase of afferent impulses from the distal ending of a pelvic vesical branch was observed. P-4 (10 mg/kg, i.v.) had no effect on the afferent impulses. When the central endings of the pelvic vesical branches were electrically stimulated, reflex discharges were noted from a pelvic vesical branch on the contralateral side. Thiopental (2 and 4 mg/kg, i.v.) markedly decreased the reflex discharge, whereas P-4 (10 mg/kg, i.v.) caused no such inhibition. These findings suggest that the inhibition of the vesico-detrusor reflex by P-4 may result from its inhibitory action on the efferent terminal of the pelvic nerve.

Effects of HSR-902, a new antispasmodic agent, on the junctional transmission of pelvic nerve ending in isolated urinary bladder was compared with those of atropine sulfate, butylscopolamine bromide, timepidium bromide and prifinium bromide. Tetrodotoxin (3 x 10(-8)g/ml) completely inhibited the contraction of isolated guinea pig urinary bladder induced by transmural stimulation (TM contraction), but hexamethonium chloride (1 x 10(-4)g/ml) and atropine sulfate (1 x 10(-5)g/ml) exhibited no inhibition and a slight inhibition, respectively. Neostigmine bromide (1 x 10(-7)g/ml) increased TM contraction, and the effect was completely inhibited by atropine sulfate (1 x 10(-5)g/ml). Antispasmodic agents (1 x 10(-7) - 1x 10(-5)g/ml), excluding HSR-902, showed slight inhibition on TM contraction. In contrast, HSR-902 (1 x 10(-6) - 1x10(-5)g/ml) increased TM contraction and/or resting tone (1 x 10(-5)g/ml). Phenoxybenzamine hydrochloride (1 x 10(-8)g/ml) and tolazoline hydrochloride (1 x 10(-5)g/ml), alpha-blocking agents, increased both TM contraction and resting tone. Increasing effects of HSR-902 on TM contraction and/or resting tone were completely inhibited by noradrenaline (1 x 10(-5)g/ml) with propranolol hydrochloride (1 x 10(-5)g/ml). These results suggested that these antispasmodic agents scarcely inhibited the junctional transmission in postganglionic cholinergic nerve ending induced by transmural stimulation of isolated guinea pig urinary bladder, and HSR-902 rather increased the transmission. Since it was also suggested that there was alpha-adrenoceptor inhibiting acetylcholine-release in the postganglionic cholinergic nerve terminal, the transmission increasing action of HSR-902 would be due to its alpha-blocking action.

Chemical sympathectomy induced by guanethidine or 6-hydroxydopamine (6-OHDA) and reserpinization were investigated by their influences on the cardiovascular system in urethane-anesthetized rats and guinea pigs and on nerve endings in the atrium or aorta and adrenaline-containing granules in the adrenal medulla. In rats, guanethidine and 6-OHDA significantly lowered the basal blood pressure, but reserpine did not. In guinea pigs, none of them affected the basal blood pressure, and with the exception of the potentiation of adrenaline-induced pressor responses, the influences of all 3 drugs on adrenaline- and tyramine-induced responses in blood pressure and heart rate were weaker than those in rats, but influences of treatments with guanethidine for 1 week were more striking than those for 5 weeks. There were significant differences between rats and guinea pigs in classified forms of nerve endings in the right atrium and of adrenaline-containing granules in the adrenal medulla or differences in the influences on the adrenal medulla by all 3 drugs. Only 6-OHDA induced injury in rat atrium. The above results suggest that there are species differences between rats and guinea pigs, not only in the chemical sympathectomized animals but also in the normal condition and that the pharmacodynamic effect of chemical sympathectomy is more prominent in rats than in guinea pigs.

General pharmacological properties of penfluridol (TLP-607) a long-acting antipsychotic drug, were examined in experimental animals and the following results were obtained. 1) TLP-607 produced a lowering of arterial blood pressure and bradycardia but had almost no effect on respiration and peripheral blood flow. 2) TLP-607 slightly hypertension induced by dopamine, adrenaline and noradrenaline, but had no effect on hypotension induced by acetylcholine and histamine. 3) Antagonistic actions of TLP-607 on such spasmogens as acetylcholine, histamine and barium chloride were slightly stronger than those of haloperidol and chlorpromazine. 4) TLP-607 had neither ganglionic nor neuromuscular blocking action. 5) TLP-607 had a slight or no effect in the following experiments; protection against stomach ulcer, activity of ileum and uterus in vivo and in vitro, urinary volume and electrolytes excretion, and gastro-intestinal propulsion. These results suggest that TLP-607 has no striking peripheral actions in experimental animals.