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A light scattering technique was developed to measure the propagation of liquid surface waves over a wide frequency range. Thermal fluctuation of liquid surface displacement excites a surface tension wave, called the ripplon, whose behavior gives information on dynamic properties of the liquid surface. A laser beam is scattered by the ripplon, and the power spectrum of the scattered light is detected with the optical beating technique, which yields the frequency and damping constant of the ripplon. Previous measurements of the ripplon have been limited to frequencies below 100 kHz. The range of measurements is extended up to 6 MHz. The dispersion relation and the damping constant were obtained over the ripplon wave number (K) range of 4*10/sup 4/ >

The critical anomaly in the complex shear modulus of an entangled polymer solution and a gel was studied. A system was constructed for measuring a complex shear modulus in the low-frequency range from 1 Hz to 500 Hz. Near the binodal line, the anomaly increases in both the real and the imaginary part of the complex shear modulus were observed in a concentrated solution of polymer. The elasticity is a result of strong entanglement. The critical anomaly in an entangled system may have a unique nature because of the elastic energy of the network. The temporal change of the complex shear modulus during phase separation can be measured using this system, since the time required for measuring the frequency spectrum is drastically shortened by applying the multifrequency excitation method. >

Cimetidine, a new histamine H2-receptor antagonist (50 or 100 mg/kg) and atropine sulfate (15 mg/kg) given intraduodenally, markedly inhibited gastric secretion in pylorus-ligated rats. Cimetidine (100 or 200 mg/kg/day) given for 10 or 12 consecutive days orally in two divided doses, significantly promoted the healing rate of both gastric and duodenal ulcers induced in rats. Atropine (30 mg/kg/day) also significantly accelerated the healing of duodenal ulcers but failed to affect gastric ulcers.

Pharmacological properties attributed to Panacis Japonici Rhizoma (PJR) in Chinese medicine in Japan in terms of its usage as a drug for gastroenteric disorders, antipyretic, antitussive, expectorant and antiinflammatory drug, were studied. Chikusetsusaponin III was especially remarkable as it had antipyretic, antitussive, expectorative and antiedemic activities, increased intestinal motility, and prevented stress ulcers. Chikusetsusaponin IV showed expectorative action, protection against stress ulcers and acceleration of intestinal motility. Chikusetsusaponin V showed antiedemic activity. The substance giving protective effect against gastric secretion was found in the butanol layer but was not recognized in the saponins. Increased effect of intestinal motility was recognized in aqueous extract.

Effects of L-glutamine on acetylsalicylic acid (ASA)-induced gastric mucosal lesions were studied in mongrel dogs. It was confirmed that when oral ASA at 1.0 or 2.0 g per dog is given in two divided doses, there is severe and consistent dose-dependent mucosal damage in the glandular portion of the stomach in fasted dogs. However, when L-glutamine 2.0 or 4.0 g per dog in two divided doses is given concomitantly with ASA 2.0 g per dog orally, the gastric irritation is significantly inhibited. Instillation of 20 mM of ASA in 100 mM HCl solution into the Heidenhain pouch of Beagle dogs produced a significant loss of H+ from the pouch and a gain of Na+ in the lumen compared with ASA-free controls. When L-glutamine (100 mM) was given concomitantly with ASA (20 mM) into the pouch, changes of electrolyte fluxes in response to ASA alone were significantly suppressed. However, 50 mM of L-glutamine had no appreciable effect on acid back diffusion caused by ASA 20 mM. The amino acid itself had little effect on the ionic movement in the pouch. Gross bleeding from the pouch treated with ASA was never observed with the concomitant dosing of ASA and L-glutamine 50 or 100 mM.

Pole-climbing and shuttle-avoidance tests were employed to study the acquisition of conditioned avoidance response (CAR) and discrimination behaviour (DB) in male Wistar rats which had been given extracts from Panax Ginseng root intraperitoneally or orally. Neither a lipid soluble fraction (GNo. 5) nor a ginsenoside Rg fraction (GRg) produced significant changes in the acquisition of CAR. GRg given intraperitoneally produced a significant acceleration in the acquisition of DB between a 500 Hz signal sound followed by an electric shock (SD) and a 1000 Hz signal sound without a shock (S delta) in rats which had learned to avoid the shock following SD at a rate of over 95%. Small doses of GNo. 5 produced a significant depression in the acquisition of DB.

Intracellular localization of histamine receptors in small intestinal smooth muscle of the cat was studied by investigating distribution of marker enzymes in the receptor rich fraction. Distribution of membrane markers coincided with that of the radiochemically labeled receptor fraction. Membrane fraction was further purified and it was concluded that the histamine receptor rich fraction is mainly composed of cell membrane. The chemical composition of the fraction lent support to this conclusion.

Pole climbing and shuttle box tests were employed to study conditioned avoidance response (CAR) and discrimination behaviour in Wistar male rats given extracts from Panax Ginseng root intraperitonealy. Neutral saponins (GNS), a water soluble fraction (GF4) which does not contain saponins, and a lipid soluble fraction (GNo. 5) inhibited CAR and discrimination ability between 500 Hz sound with electric shock (SD) and 1000 Hz sound without shock (SΔ). Small doses of GNo. 5 and ginsenoside Rg fraction (GRg) produced a slight shortening of the response latency (RL) to the conditioned stimulus in CAR. GNo. 5 produced the incorrect response to SΔ. Significant changes in the extinction of CAR were not evident with any fraction. Data from these tests indicate that Panax Ginseng root contains at least three sedative compounds.

The relationship between chemical components of the injured portion in acetic acid ulcer and ulcer healing, and the influence of anti-inflammatory drugs on the ulcer were investigated herein. The hexosamine content in the corpus of normal rat stomach was decreased by a 20 day administration of Na salicylate or phenylbutazone. Healing of 10% acetic acid ulcer was delayed remarkably by Na salicylate or phenylbutazone, and hexosamine in the injured portion of the ulcer was decreased simultaneously. Steroidal anti-inflammatory drugs delayed healing of the ulcer, especially in the early stage administration, where hexosamine and hydroxyproline decreased significantly. Sodium salicylate, on the contrary, delayed the ulcer healing in the early and also later stage administration. Lowered hexosamine content in the mucosa and fall of hydroxyproline content in the stroma of the injured portion paralleled the increase of area index and grade index, respectively. In the delayed healing of the ulcer with anti-inflammatory drugs, it was clarified that changes of tissue components of the injured portion immediately after the ulcer formation play an important role in ulcer healing.

Antiulcer effects of N-acetyl-L-glutamine aluminum complex (KW-110) were studied in experimental gastric and duodenal ulcer models in the rat, comparing its effect to that of atropine sulfate. It was found that KW-110, given orally 3 times daily for 8 days, had an accelerating activity on the healing process of duodenal ulcer whereas atropine sulfate, given s.c. twice daily for 8 days at a glutamine dose to Sufficiently suppress gastric secretion, had a significant effect. In addition, KW-110 showed remarkable effects on prevention of acutely induced experimental gastric ulcers. In regard to the Shay ulcer or aspirin-induced gastric lesions, KW-110 showed enhanced effects which exceeded the apparently maximum effects of atropine sulfate, even though the dosage of the former was much higher than that of the latter. While atropine sulfate completely inhibited the stress-induced gastric lesions, KW-110 also revealed a strong inhibition on the lesions.

Responses of the perfused forelimb paw small vein in anesthetized dog to vasoactive agents including serotonin, histamine, bradykinin, acetylcholine and epinephrine were investigated together with their modification by anti-inflammatory drugs. Venous perfusion with blood frequently caused venospasms which could not be attenuated by anesthetics, gallamine or phentolamine. In perfusion experiments both with blood and with Krebs-bicarbonate solution, close i.v. injections of epinephrine, serotonin and acetylcholine caused marked venoconstrictions (threshold doses in blood perfusion experiments, about 1, 3 and 300 ng, respectively), whereas bradykinin and histamine produced only weak constrictive responses even in large doses of more than 3 ng. Close i.v. injections of non-steroidal anti-inflammatory drugs, i.e. phenylbutazone, 150 μg/min, sodium salicylate, 500 jug/min, indomethacin, 50 μg/min, aminopyrine, 300 μg/min and benzydamine, 10 μg/min, nonspecifically depressed the venoconstrictor responses to epinephrine, serotonin, acetylcholine, bradykinin and histamine. A steroidal anti-inflammatory drug, hydrocortisone, however, tended to enhance the effect of epinephrine with no influence on the effects of the other vasoactive agents. The results suggest that the inhibitory effects of non-steroidal antiinflammatory drugs on the venoconstrictor responses to the vasoactive agents may contribute to their anti-inflammatory activity through the inhibition of facilitated vascular permeability due to the rise in hydrostatic pressure of the fine blood vessels.

Antioxytocin activities of bile salts and their effects on phosphodiesterase (PDE) activities and the intracellular level of cyclic AMP in the rat uterus were investigated, and the mode of action of the bile salts was compared with that of papaverine or Aspaminol. The bile salts, chenodesoxycholate, desoxycholate, ursodesoxycholate and cholate significantly decreased PDE activities and a good relationship between the PDE activities and the antioxytocin activities of the bile salts was observed. Chenodesoxycholate and desoxycholate significantly increased the intracellular level of cyclic AMP in the rat uterus. The exogenously applied CaCl2 potentiated the inhibitory responses of the rat uterus to papaverine, aminophylline responses of the rat uterus to papaverine, aminophylline and bile salts, while the inhibitory response to Aspaminol was greatly reduced by excess CaCl2. These results indicate that the antioxytocin action of the bile salts may be exerted through an increase in the intracellular level of cyclic AMP. Further, the results support the theory that there are two mechanisms for "papaverine-like" antipasmodics.

The beta-adrenergic receptors in the taenia isolated from the guinea pig caecum were irreversibly inactivated by photoaffinity labeling with l-isoprenaline and 2-(2-hydroxy-3-isopropylaminopropoxy)iodobenzene. The photoinactivation was elimination in the presence of protectors of the receptors. Photoinactivation caused a considerable parallel shift in the concentration-action curve of l-isoprenaline. The results possibly point to a certain receptor reserve for l-isoprenaline.

The intracellular level of cyclic AMP in the taenia from the guinea pig caecum was significantly increased by isoprenaline in a dose-dependent manner. Papaverine also increased the intracellular cyclic AMP level, but a synthetic antispasmodic agent, Aspaminol (1,1-diphenyl-3-piperidinobutanol hydrochloride) did not modify it. The results suggest that there are two mechanisms for the so-called papaverine-like actions. The increase in the intracellular cyclic AMP concentration produced by isoprenaline was prevented by propranolol. In taenia depolarized by KCl, papaverine caused relaxation but isoprenaline did not. This difference can be explained by the observation that the intracellular cyclic AMP level in the KCl-depolarized taenia is increased by papaverine but not by isoprenaline.

Effects of 5-hydroxytryptamine, sodium picrate, caerulein and pentagastrin on the electrical activities obtained from Auerbachs plexus in the guinea pig ileum were investigated. The drugs used increased the spike frequency and increase of the spike frequency induced was inhibited by morphine but not by atropine and hexa-mcthonium. The muscle spikes obtained simultaneously were inhibited by atropine. These facts indicate that the drugs used stimulate Auerbachs plexus and accelerate the acetylcholine release from the cholinergic post-ganglinoic nerve endings. The sites of action of morphine are also discussed.

L-Glutamine given orally at 750 mg/kg significantly reduced the formation of gastric mucosal lesions induced by aspirin at 100 mg/kg at 1, 3, and 7 hours in pylorus-ligated rats. L-Glutamine markedly inhibited the loss of H+ and a corresponding increment of Na+ through the aspirin-damaged mucosal barrier, which suggests inhibition of acid back diffusion as the mechanism of action. In vagotomized rats, the diffusion of H+ from the instilled acid solution into the gastric mucosa and outflux of Na+ from the mucosa into the lumen was so strong that aspirin could not show any acceleration of a back diffusion of H+ in contrast to the aspirin-free group. However, L-Glutamine given with or without aspirin inhibited the group. However, L-Glutamine given with or without aspirin inhibited the back diffusion of H+ instilled into the vagotomized rat stomach.

An oral dosing of either acetylsalicylic acid (ASA) or taurocholic acid (TCA) to pylorus-ligated rats subjected to water-immersion stress produced severe damage to the gastric musoca in contrast to the irritation observed in non-stressed ones. The irritative activity of ASA or TCA on gastric mucosa under stress was dose-dependent. Stress itself (23 degrees C, 7 hr) did not induce any appreciable changes in gastric mucosa under stress wasic mucosa of rats. L-glutamine, given together with SAS or TCA, significantly prevented the potentiated development of SAS- or TCA-induced gastric lesions in stressed rats. L-glutamine also prevented in varying degrees the reduction of acid and increment of Na+ ion in gastric juice accumulated in stressed rats in response to ASA or TCA.

The anti-inflammatory activities of hederagenin and crude saponin isolated from Sapindus mukorossi GAERTN were investigated utilizing carrageenin-induced edema, granuloma pouch and adjuvant arthritis in rats. The effects of these agents on vascular permeability and acetic acid-induced writhing in mice were also examined. In some experiments, the results were compared with those obtained with saikogenin A, crude platycodin, platycodigenin and oleanolic acid. Anti-inflammatory activity on carrageenin edema was observed with i. p. and p. o. administered crude saponin, while hederagenin and the other agents used showed activity only when administered i. p. Hederagenin, 100 and 200 mg/kg p. o. per day for 7 days, showed no significant inhibitory effect on granuloma and exudate formations in rats, while crude saponin, 100 and 200 mg/kg p. o., showed significant effects. Crude saponin, 200 mg/kg p. o. per day for 21 days, significantly inhibited the development of hind paw edema associated with adjuvant arthritis in rats, but hederagenin, 50-200 mg/kg p. o., did not. Crude saponin, 400 mg/kg p. o., inhibited the increase in vascular permeability and the number of writhings induced by acetic acid in mice. The results suggest that hederagenin and crude saponin, as well as the other agents used, show some degree of anti-inflammatory activity, especially in the case of saponin.

A chronic gastric ulcer model was produced in rats by the subserosal injection of 20 % acetic acid solution (0.015 ml) in order to examine whether (1) acetylsalicylic acid (ASA) irritates the chronic

Mitochondrial, microsomal and soluble fractions separated from the guinea pig taenia and from the dog longitudinal smooth muscle were used as phosphodiesterase preparation. Each preparation had low and high Km values, indicating the existence of at least two kinds of phosphodiesterase. Papaverine and Aspaminol (1, 1-diphenyl-3-piperidinobutanol hydrochloride), hydralazine, caffeine Na benzoate and aminophylline were used at test drugs. Aspaminol had little inhibitory effect on phosphodiesterase. Ki value of papaverine almost equalled the concentration (M) which was necessary to produce 50% relaxation. Relaxation of the guinea pig taenia by papaverine was preceded by an increase of intracellular cyclic AMP,. Therefore, the action of papaverine is likely to be mediated by an increase in cyclic AMP, which is caused by inhibition of the phosphodiesterase-catalyzed breakdown of cyclic AMP. There was little correlation between relaxing activities of the drugs used and their antiphosphodiesterase activities. Relaxation of the smooth muscle induced by the smooth muscle relaxants excepting papaverine is not due to inhibition of phosphodiesterase.

Antihypertensive activity of orally administered methyl O-(4-hydroxy-3-methoxycinnamoyl)reserpate (CD-3400) was examined and compared with such activity of reserpine and its related agents in conscious hypertensive rats. CD-3400, 4–16 mg/kg p.o., produced a marked antihypertensive effect lasting 6 hr and a slight decrease in heart rate in spontaneously hypertensive rats (SHR). Reserpine, 1–4 mg/kg, rescinnamine, 4–16 mg/kg, and syrosingopine, 8–32 mg kg p.o., produced effects similar to those of CD-3400. The order of antihypertensive activities of the agents was as follows: reserpine>CD-3400═rescinnamine>syrosingopine. In renal hypertensive rats and deoxycorticosterone hypertensive rats, CD-3400 and rescinnamine, 4–16 mg/kg, and reserpine, 1–4 mg/kg p.o., also produced an antihypertensive effect and the order of potency was as follows: reserpine>rescinnamine≧CD-3400. Repeated administrations of CD-3400, 2–12 mg/kg/day p.o., for 14 days, to SHR produced the marked constant antihypertensive effects during the administration period. The order of the potency was as follows: reserpine> rescinnamine>CD-3400. CD-3400 possessing a sustained antihypertensive activity may be prescribed in cases when long-term therapy is required for hypertensive patients.

Effects of L -glutamine on gastric lesion models in rats and guinea pigs were studied. Shay ulceration in rats was not inhibited by oral L -glutamine. Although stre

Studies were made on tritiated histamine binding to the receptor-rich membrane fraction and solubilized sites and its displacement by various drugs. H1-Agonists and antagonists displaced histamine most effectively. A H2-agonist and atropine were less effective and propranolol, phentolamine and imidazole acetic acid had little effect. The solubilized binding sites showed the same specificity of binding as the membrane fraction. Membrane fragments had two binding constants, whereas solubilized sites had only one. Solubilized sites bound similar amounts of histamine and dibenamine: the latter was applied to intact tissue under conditions which would presumably cause specific binding to histamine receptors. These binding characteristics show that the method used was adequate for purification of histamine receptors from smooth muscle of cat small intestine.

A mitochondrial fraction was isolated from rat uterine smooth muscle. The effect of papaverine (3 × 10−6, 10−5, 3 × 10−5, 10−4 M) on Ca2+ accumulation by the fraction was studied. The effect of papaverine was changed by using different substrates for Ca2+ accumulation. Papaverine inhibited the Ca2+ accumulation supported by glutamate plus ATP concentration-dependently. The Ca2+ accumulation supported by ATP alone was also inhibited. On the other hand, the Ca2+ accumulation supported by succinate and ATP was increased by papaverine. The effect was not concentration-dependent; papaverine (3 × 10−5 M) was the most effective concentration for the effect with a shorter incubation (2 min).

The maximum contraction induced in taenia from the guninea pig caecum by a cholinergic stimulant, butyltrimethylammonium (BuTMA) was relaxed by papaverine (10(-4) M) but not by l-isoprenaline (5 X 10(-7) M). The concentrations used relaxed the taenia completely in the absence of BuTMA. BuTMA (10(-4) M) decreased the increase of cyclic AMP caused by isoprenaline but not that due to papaverine. Futhermore, photoinactivation of the beta-adrenoceptors by l-isoprenaline was not observed on the taenia contracted by BuTMA (10(-4) M). These results suggest that l-isoprenaline does nto interact with the beta-adrenoceptors in the taenie contracted by the high concentration of BuTMA.

The effects of metiamide, a histamine H2-receptor antagonist, and propranolol, a beta-adrenergic blocking agent, on gastric secretion were studied in anesthetized dogs. Metiamide, 1.45 mg/kg i.v., markedly inhibited the gastric secretion induced by a continuous i.v. infusion of tetragastrin (8 microng/kg-hr), histamine dihydrochloride (160 microng/kg-hr), or methacholine bromide (100 microng/kg-hr). Propranolol 0.5 or 1.0 mg/kg i.v. produced a significant potentiation of tetragastrin-induced gastric secretion but no influence of the secretion induced by methacholine. Propranolol at 5 or 10 mg/kg i.v. produced a slight reduction of the tetragastrin-induced secretion and a significant reduction of methacholine-induced secretion. Histamine-induced gastric secretion was not affected by propranolol at either 1 and 10 mg/kg i.v. These findings lend support to the hypothesis that interactions among histamine, gastrin and acetylcholine receptors do occur though the degree would not be the same in all directions.

Water-immersion stress for 7, 14, or 20 hr consistently induced linear or punctate stress ulcers (mucosal erosions) in the corpus of the stomach in intact rats. When the pylorus of the stomach had been ligated prior to stressing, the stress ulcers changed their morphological feature (mainly punctate and in one place elongated) and location (both in corpus and antrum). Histologically, the stress ulcer developed in the proximal antrum of pylorus ligated rats and penetrated into the muscularis mucosa. Sodium bicarbonate, chlorpromazine, hexamethonium, atropine, metiamide, and bilateral vagotomy markedly inhibited the stress ulcers which developed in the pylorus-ligated rats. Phentolamine and propranolol hardly affected the development of stress ulcers. Amylopectine evoked a new type of stress ulcer in the corpus when it was given to the pylorus-ligated rats.

The effects of 5-hydroxytryptamine and morphine on the stomach motility were determined in in situ experiments. 5-Hydroxytryptamine and morphine inhibited stomach motility of unanaesthetized cats but did produce a slight contraction of the stomach of anaesthetized cats. In unanaesthetized rabbits, 5-hydroxytryptamine caused a contraction, followed by an inhibition of motility, and morphine depressed motility. The 5-hydroxytryptamine-induced contraction is a direct action on smooth muscle and the inhibition of spontaneous movement due to 5-hydroxytryptamine may be, in part, mediated through catecholamine-release and in part, result from paralysis of the receptors for 5-hydroxytryptamine in the cholinergic nerves in the stomach. In anaesthetized rabbits, 5-hydroxytryptamine produced contraction and morphine had no effect. In unanaesthetized guinea pigs, 5-hydroxytryptamine caused a contraction and morphine abolished spontaneous movement of the stomach. In anaestetized guinea-pigs, 5-hydroxytryptamine caused contraction and morphine produced no effect. The 5-hydroxytryptamine-induced contraction of the guinea pig stomach is indirect. From these results it is concluded that the differences in the modes of actions of 5-hydroxytryptamine and morphine on gastric motility are related to differences in species and experimental conditions such as anaesthesia.

Relationship between contraction and cyclic AMP levels induced by BaCl2 was examined in the longitudinal smooth muscle isolated from guinea pig ileum. BaCl2 3 X 10(-3)M caused a fast initial contraction, often followed by a gradual decrease of the contractile state. There was an increase in the tissue cyclic AMP 7 min or 14 min after the application of Ba. A phosphodiesterase activator imidazole reinforced the later phase of contraction by Ba and inhibited the increase in cyclic AMP. These results indicate that there is still a positive correlation between relaxation and increase in cyclic AMP and that an inhibitory action mediated by cyclic AMP is veiled behind the Ba contraction. Furthermore, these results may be interpreted by assuming that strong Ba contraction operates a feedback mechanism and that the feedback mechanism is associated with cyclic AMP increase. Indomethacin, an inhibitor of prostaglandins synthesis, little influenced the Ba-induced increase in cyclic AMP and rather inhibited the Ba contraction. Propranolol, a beta-adrenergic blocking agent, failed to exert influence on the Ba contraction. Based on these facts, it is suggested that the increase in cyclic AMP is not mediated by prostaglandins or catecholamines.

We found that there are strain differences in aspirin-induced ulceration in pylorus-ligated rats; the ulcer indices varied, from high to low, in the following order: Donryu greater than Sprague-Dawley greater than Wistar. Several experiments including analysis of gastric contents or ionic flux, determination of serum aspirin esterase activity, absorption of aspirin from the stomach, prothrombin time and hexosamine content in gastric mucosa and juice were performed to elucidate the origin of the differences. A significantly higher acid output in Donryu rats, and higher hexosamine content in the gastric mucosa of Wistar rats were noted. However, it appears unlikely that these factors only contribute to the marked strain difference in aspirin-induced ulcers. The possible different sensitivity of gastric mucosal cell itself to aspirin must be considered.

There have been some articles in regard to the pharmacological study on the extraocular muscles. Katz and Eakins (1) reported the in situ effect of drugs on electrically stimulated extraocular muscle of cats, and Kern (2, 3) studied the effect of sympathomimetic amines on the isolated extraocular muscles. However, there has been no publication, to our knowledge, in regard to the electrical stimulation of the isolated extraocular muscle-nerve preparations. The investigations on the neuromuscular junction in the extraocular muscle were generally carried out in the in situ experiments. In the in situ experiments a part of responses of the extraocular muscles to drugs may be due to secondary effects accompanied with responses of the intraocular muscles to the drugs. In the present study, the effects of drugs on the electrically stimulated extraocular muscle-nerve preparations isolated from rabbits were investigated and were compared with actions of the drugs in the in situ experiments. Furthermore, actions of drugs on the isolated extraocular muscles were examined.

(1) Tracheal strip preparation was proved to respond very sensitively to acetylcholine (ACh) and histamine. It is more suitable to test drug action on tracheal smooth muscle than tracheal chain. (2) From the present experimental results and on applying Ferguson's rule, the papaverine-like antispasmodic action, which is tested ordinarily against barium contraction of ileum, must be divided into two categories ; (a) the nonspecific inhibitory action, which is exerted by some physicochemical property of non-ionized molecules and can be tested on tracheal muscle, and (b) the specific unsurmountable inhibitory action, which is exhibited by ionized molecules of strong bases and can be tested on ileum. (3) Neutral esters such as isoamyl esters and weak bases such as papaverine exist as non-ionized molecules in physiological pH, and they have only nonspecific inhibitory action on any smooth muscles. Strong bases such as tertiary amines are ionized as much as 90% of the total amount in physiological solution. They exert specific but unsurmountable inhibitory action on ileum by their cation and exhibit non-specific action on tracheal muscle through their neutral base.

The effects of five diphenylalkanolamine derivatives, including YS 3635, YS 3636, YS 3632, YS 3623 and YS 3423, on the coronary and hindquarter vascular beds in anesthetized dogs were studied and compared with those of glyceryl trinitrate and papaverine. These five derivatives in doses of 62.5 to 1000μg i.a. reduced coronary and hindquarter vascular resistances, and the effects were in the following order : YS 3423>YS 3623> papaverine>YS 3632>YS 3635>YS 3636 in the coronary, and YS 3423> papaverine>YS 3623>YS 3635>YS 3632>YS 3636 in the hindquarter vascular beds. Three derivatives, YS 3423, YS 3623 and YS 3635 having a relatively potent vasodilating effect were further examined. These compounds, 1 mg/kg i.v., also showed an increase in coronary and hindquarter blood flows, concomitantly with a transient hypotension, sustained decrease in heart rate and increase in cardiac output. The vasodilating effect of the diphenylalkanolamine derivatives studied appears to show a direct and non-specific effects on the peripheral blood vessels as is the case of glyceryl trinitrate or papaverine.