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Biomedical subjects

H Maeno

Publications and source records attributed to H Maeno.

At least 55 records · Page 3Linked to original sources
PubMed1982

Antihypertensive and adrenoceptor blocking properties of new sulfonamide-substituted phenylethylamines.

Studies on the structure-activity relationship using 9 new 3-sulfamoylphenylethylamines revealed that YM-09538, YM-09649 and YM-09686 were competitive antagonists at both beta- and post-synaptic alpha-receptors. The following order of adrenoceptor blocking activities was obtained : propranolol greater than labetalol greater than YM-09538 greater than YM-09649 greater than YM-09686 for beta-receptors and prazosin greater than YM-09686 greater than YM-09649 greater than YM-09538 greater than phentolamine greater than labetalol for postsynaptic alpha-receptors. In contrast to phentolamine, three YM-compounds showed low affinities for presynaptic alpha-receptors similar to prazosin and labetalol. These antagonists except propranolol effectively lowered blood pressure in conscious SHR and their relative effectiveness parallels the postsynaptic alpha-blocking activity. At hypotensive doses, phentolamine markedly and prazosin, YM-09686 and YM-09649 moderately increased heart rate, whereas YM-09538 and labetalol failed to increase the rate. These results indicate that the postsynaptic alpha-blocking activity of YM-compounds contributes to their hypotensive activities and that both beta-blocking and low presynaptic alpha-blocking activities contribute to attenuation of the tachycardia.

Animals↗
PubMed1982

Effect of a new potent H2-blocker, 3-]]]2-[(diaminomethylene)amino]-4-thiazolyl]methyl]-thio]-N2-sulfamoylpropionamidine (YM-11170) on gastric secretion induced by histamine and food in conscious dogs.

The inhibitory effect of a new H2-receptor antagonist YM-11170 on gastric acid response to histamine and food was compared with that of cimetidine in the conscious dog with a Heidenhain pouch. When given intravenously at a steady state of gastric secretion by continuous infusion of histamine. YM-11170 was 42 times more potent and 1.3 times longer-lasting (p less than 0.05) than cimetidine in reducing the total acid output. The higher potency of YM-11170 than that of cimetidine was also demonstrated in oral antisecretory tests with histamine. The oral ED50 relative to i.v. ED50 as an indirect indication of absorption rate of the drugs was 2.9 for YM-11170 and 2.7 for cimetidine. The secretory response to food stimulation was also antagonized by oral administration of YM-11170 with 40 times greater potency than that of cimetidine. The antisecretory effects of the drugs on the histamine-induced gastric secretion were characterized by a marked decrease in the secretory volume. No behavioral change was observed in association with the H2-blockers. These results indicate that YM-11170 is a very potent inhibitor of gastric acid secretion and also suggest that the absorption rate of YM-11170 from the gastro-intestinal tract is similar to that of cimetidine.

Animals↗
PubMed1982

Effect of a new potent H2-blocker, 3-[[[2-(diaminomethylene)amino]-4-thiazolyl]methyl]thio]-N2-sulfamoyl propionamidine (YM-11170), on gastric secretion, ulcer formation and weight of male accessory sex organs in rats.

A new H2-blocker, 3-[[[2-[(diaminoethylene)amino]-4-thiazolyl]ethyl]thio]-N2-sulfamoyl propionamidine (YM 11170) inhibited gastric secretion of both acid and pepsin, when given intraduodenally to pylorus-ligated rats. The effectiveness of YM-11170 in the inhibition of acid output was 50 times as potent as that of cimetidine. The higher antisecretory activity of YM-11170 than that of 1-cyano-2-methyl-3-[2-[[(5-methylimidazol-4-yl)-methyl]thio]ethyl]guanidine (cimetidine) was also demonstrated by oral or i.v. administration. The development of gastric ulcer induced by either indometacin or acetylsalicylic acid in rats was markedly suppressed by YM-11170 with higher potency than by cimetidine. In castrated and androgenized rats, the decrease in the seminal vesicle and ventral prostate weights was not observed after treatment with YM-11170. These results suggest that YM-11170 is a potent antisecretory agent without antiandrogenic activity.

Androgen Antagonists↗
PubMed1981

Neuroleptic properties of cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-09151-2) with selective antidopaminergic activity.

A new benzamide, cis-N-(1-benzyl-2-methylpyrrolidin - 3 - yl) - 5 - chloro - 2 - methoxy - 4 - methylaminobenzamide (YM-09151-2) exhibited more potent and longer-lasting inhibitory effects on apomorphine-induced behaviours (stereotyped behaviour, emesis and hypothermia), and methamphetamine-induced stereotyped behaviour, conditioned avoidance response and open field behaviour, conditioned avoidance response and open field behaviour than either structurally similar benzamides (YM-0850 and sulpiride) or classical neuroleptics [chlorpromazine (CPZ) and haloperidol(HPD)]. Such inhibitory effects of YM-09151-2 relative to cataleptogenicity were greater than those of CPz and HPD. In contrast, sulpiride elicited few of the neuroleptic effects described above. YM-09151-2, a potent inhibitor for dopamine-sensitive adenylate cyclase (Ki: 3.0 nM) reduced, in a selective manner, the binding of [3H]dopamine to the dopamine D1 receptor (Ki:4.8 nm) associated with adenylate cyclase rather than to the dopamine D2 receptor (Ki: 0.98 microM) independent of adenylate cyclase. Sulpiride, on the contrary, inhibited only the binding to the dopamine D2 receptor, CPZ and HPD antagonized [3H]dopamine nonselectively at the two distinct dopaminergic receptors. These results suggest that YM-09151-2 is a potent and long-lasting neuroleptic with a highly selective blocking action on the dopamine D1 receptor.

Animals↗
PubMed1981

A possible mechanism for relaxation of rat uterine smooth muscle by nicardipine hydrochloride (YC-93), a new potent vasodilator.

A new potent vasodilator, nicardipine hydrochloride inhibited oxytocin-induced contraction of rat uterus dose-dependently with an increase in the intracellular cyclic AMP level at the onset of relaxation. Dibutyryl cyclic AMP and papaverine, an inhibitor of cyclic AMP phosphodiesterase (PDEase), also inhibited the contraction. Nicardipine inhibited competitively PDEase in homogenates of rat uterus which exhibited apparently two Km values for cyclic AMP (3.6 micro M and 67.3 micro M) with the Ki of 5.3 micro M and 13.2 micro M, respectively, but had no effect on adenylate cyclase. Nicardipine enhanced calcium uptake by rat uterine microsomes, at concentrations which inhibited oxytocin-induced contraction in the same manner as cyclic AMP. The maximal stimulation by nicardipine of the microsomal calcium uptake was identical substantially to that by cyclic AMP, and both were not additive. Cyclic AMP was also accumulated during the uptake reaction in the presence of nicardipine. On the contrary, neither myosin ATPase nor microsomal Ca2+-dependent ATPase was inhibited directly by nicardipine. These results suggest that the inhibition of oxytocin-induced contraction of rat uterus by nicardipine may be due to an enhancement of microsomal calcium uptake, mediated by cyclic AMP accumulated through the inhibition of PDEase.

Adenosine Triphosphatases↗
PubMed1981

[Central pharmacological effects of YPG-209 (16(S)-methyl-20-methoxy-prostaglandin E2) (author's transl)].

Central pharmacological effects of YPG-20 were examined in comparison with those of PGE2 (prostaglandin E2). Spontaneous motor activity and exploratory movement in mice were inhibited by oral administration of YPG-209 in a dose of 10 micrograms/kg. These inhibitions seemed to involve factors different from those related to the central nervous system, e.g. intestinal movement. Thiopental-induced sleeping time in mice was prolonged by oral administration of YPG-209 in a dose of 300 micrograms/kg. On the other hand, spontaneous EEG and EEG arousal response in gallamine-immobilized cats were not affected by intravenous administration of YPG-209 in a dose of 100 micrograms/kg. Mice taming effect, rota rod performance and drug- or electroshock-induced convulsions were not affected by oral administration of YPG-209 in a dose of 3 mg/kg. Methamphetamine-induced lethality in mice was inhibited by subcutaneous administration of YPG-209 in a dose of 5 mg/kg. Normal rectal temperature in mice was lowered by oral administration of YPG-209 in a dose of 5 mg/kg. Normal rectal temperature in mice was lowered by oral administration of YPG-209 in a dose of 100 micrograms/kg. The central pharmacological actions of PGE2 were qualitatively similar to those of YPG-209, but the potencies of central actions of PGE2 were less than those of YPG-209

Animals↗
PubMed1980

Rectal absorption of insulin suppositories in rabbits.

When insulin solutions (100 U kg-1) at various pH values were placed in the rectum of rabbits, a large decrease in blood glucose concentration was observed except at the pH close to the iso-electric point of insulin. The effect of surface-active agents on the rectal absorption of insulin was examined by measuring the blood glucose concentration after the administration of 2 or 5 U kg-1. Non-ionic ether type, anionic, cationic and amphoteric surfactants as well as bile acids increased the absorption. The optimal effect with suppositories was reached with the addition of 1% polyoxyethylene (9) lauryl alcohol ether. Insulin suppositories containing agents enhancing rectal absorption were compared with the insulin for intravenous, intramuscular and subcutaneous injection. The changes of blood glucose and plasma immuno-reactive insulin concentration after rectal administration of insulin were similar to those after intravenous injection.

Animals↗
PubMed1980

Inhibition of hypersensitivity reactions by 16(S)-methyl-20-methoxy-PGE2 (YPG-209) in animals.

The effects of 16(S)-methyl-20-methoxy-PGE2 (YPG-209) on hypersensitivity reactions were investigated in the rat, guinea-pig and mouse. Intravenously administered YPG-209 was 150 times as potent as disodium cromoglycate (DSCG) in the inhibitory effect on the IgE(mouse)-mediated 24 hr rat PCA. When administered intravenously to guinea-pigs, YPG-209 inhibited significantly the IgE (guinea-pig)-mediated 8 day guinea-pig PCA, whereas DSCG exhibited no significant inhibitory effects. The oral doses of YPG-209 diminished both histamine and 5-hydroxytryptamine hypersensitivity of the Bordetella pertussis-treated mice. These results suggest that YPG-209 exhibits not only the prevention of mediator release but also the antimediator effect in laboratory animals.

Animals↗
PubMed1979

Lack of effect of levallorphan on analgesia induced by intraventricular application of porcine calcitonin in mice.

Intraventricular administration to mice porcine calcitonin (10 U/kg) as well as of morphine (3 microgram/kg) elevated the threshold pressure of stimuli applied to the base of the tail as assessed by squeaking, struggling or biting, all of which were regarded as manifestations of pain sensation in the animals. Pretreatment with an opiate antagonist, levallorphan (30 mg/kg i.p.) showed no influence upon the analgesic effect of calcitonin, though it completely antagonized the effect of morphine. The results suggested that a peptide hormone, calcitonin, exerted its analgesic action in a manner distinct from the narcotic analgesic.

Analgesics↗