Dose-intensive chemotherapy with syngeneic peripheral blood stem cell support for poor risk germ cell tumor of extragonadal origin: a case report.

A variety of regimens of high-dose chemotherapy with hematopoietic stem cell support for poor risk germ cell tumors have been established. However, a series of chemotherapy steps carried out prior to the harvest sometimes leads to an insufficient number of peripheral blood stem cells. Here, we report a case of a patient who successfully underwent high-dose chemotherapy for the treatment of poor risk extragonadal germ cell tumor by receiving peripheral blood stem cell transplantation donated from his genomically identical twin brother.

A novel 5-HT3 receptor agonist, YM-31636, increases gastrointestinal motility without increasing abdominal pain.

We examined the effects of YM-31636 (2-(1H-imidazol-4-ylmethyl)-8H-indeno[1,2-d]thiazole monofumarate), a novel 5-HT3 receptor agonist, on gastrointestinal functions including visceral pain reflex in rats. Injection of YM-31636 increased the number of fecal pellets. This effect was completely inhibited by ramosetron, a 5-HT3 receptor antagonist.

Pharmacological profile of YM-31636, a novel 5-HT3 receptor agonist, in vitro.

We investigated the in vitro pharmacological profile of YM-31636 (2-(1H-imidazol-4-ylmethyl)-8H-indeno[1,2-d]thiazole monofumarate). In cloned human 5-HT3A receptors, YM-31636 had a pKi value of 9.67 vs.

Pharmacological properties of a novel gastrointestinal prokinetic benzamide selective for human 5-HT4 receptor versus human 5-HT3 receptor.

Binding properties of gastrointestinal prokinetic benzamides for both cloned human 5-hydroxytryptamine (5-HT)3 receptors and cloned human 5-HT4 receptors were examined and pharmacological properties of YM-53389{(+)-(S)-2-chloro-5-methoxy-4-[5-(2-piperidylmethyl)-1,2, 4-oxadiazol-3-yl]aniline monohydrochloride} were characterised in animals. Cisapride, renzapride and zacopride inhibited specific binding of [3H]ramosetron to cloned human 5-HT3 receptors, with Ki values of 684, 7.64 and 0.

Participation of a cholinergic mechanism in 5-hydroxytryptamine (5-HT)3 and 5-HT4 receptor-mediated stimulation of gastric emptying in rats.

The participation of a cholinergic mechanism in 5-hydroxytryptamine (5-HT)3 and 5-HT4 receptor-mediated stimulation of gastric emptying in rats was investigated. The selective 5-HT3 receptor antagonists ramosetron (YM060, 0.1-10 micrograms/kg i.

Effects of gastroprokinetic agents on gastroparesis in streptozotocin-induced diabetic rats.

The influence of diabetic hyperglycemia on solid gastric emptying in rats was examined. Diabetes was produced by streptozotocin (STZ, 40 mg/kg i.v.

Effect of a selective 5-HT3 receptor agonist on gastric motility in fasted and fed dogs.

The effect of m-chlorophenylbiguanide, a selective 5-HT3 receptor agonist, on gastric antral motility was investigated in conscious dogs with a force transducer implanted chronically. m-Chlorophenylbiguanide (0.1-1 mg/kg i.

Compounds possessing 5-HT3 receptor antagonistic activity inhibit intestinal propulsion in mice.

The role of 5-HT3 receptors in the control of intestinal propulsive activity was investigated in mice by a simple method in which the time taken for excretion of the head of an orally administered non-absorbable marker (whole gut transit time) was measured. Selective 5-HT3 receptor antagonists ramosetron (YM060) at 0.01-0.

Characterization of 5-hydroxytryptamine (5-HT) receptor subtypes influencing colonic motility in conscious dogs.

We examined the effects of exogenous 5-hydroxytryptamine (5-HT) and selective 5-HT receptor agonists and antagonists on proximal, middle and distal colonic motility in conscious fasted dogs with extraluminal force transducers implanted chronically. 5-HT (0.003-0.

Characteristics of inhibitory effects of serotonin (5-HT)3-receptor antagonists, YM060 and YM114 (KAE-393), on the von Bezold-Jarisch reflex induced by 2-Methyl-5-HT, veratridine and electrical stimulation of vagus nerves in anesthetized rats.

We evaluated the inhibitory effects of YM060 [(R)-5-[(1-methyl-1H-indol- 3-yl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole monohydrochloride] and YM114 (KAE-393) [(R)-5-[(1-indolinyl)carbonyl]-4,5,6,7-tetrahydro-1H- benzimidazole monohydrochloride] on the von Bezold-Jarisch reflex (BJR) induced by 2-methyl-5-HT, a selective serotonin (5-HT)3-receptor agonist; veratridine, which stimulates chemoreceptors and baroreceptors; and electrical stimulation of vagal efferent nerves in anesthetized rats. Results were compared with those of ondansetron and granisetron. 2-Methyl- 5-HT (5-160 micrograms/kg, i.

Effect of serotonin (5-HT)3-receptor antagonists YM060, YM114 (KAE-393), ondansetron and granisetron on 5-HT4 receptors and gastric emptying in rodents.

We investigated the effects of YM060 [(R)-5-[(1-methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazol e hydrochloride] and YM114 (KAE-393) [(R)-5-[(2,3-dihydro-1-indolyl)-carbonyl]-4,5,6,7-tetrahydro-1H- benzimidazole hydrochloride] on 5-HT4 receptors and gastric emptying in normal and cisplatin-treated rats and compared results with those for ondansetron and granisetron. YM060, YM114, ondansetron and granisetron dose-dependently inhibited the specific binding of [3H]-GR113808 ([[1-[(2-methylsulphonyl)amino]ethyl]-4-piperidin-yl]methyl 1-methyl-1H-indole-3-carboxylate) in guinea pig striatum, with pKi values of 5.53, 5.

Gastrin receptor antagonist YM022 prevents hypersecretion after long-term acid suppression.

Female rats were treated orally for 13 wk with YM022 (300 mumol.kg-1.day-1) and with omeprazole (400 mumol.

Species difference in the 5-hydroxytryptamine3 receptor associated with the von Bezold-Jarisch reflex.

Species differences in the 5-hydroxytryptamine (5-HT)3 receptor among anesthetized rats, mice, rabbits, ferrets, dogs and guinea-pigs were examined in the transient bradycardia induced by i.v. injection of 5-HT (the von Bezold-Jarisch reflex).

Comparative study of the affinities of the 5-HT3 receptor antagonists, YM060, YM114 (KAE-393), granisetron and ondansetron in rat vagus nerve and cerebral cortex.

The 5-HT3 receptor blocking properties of YM060, YM114 (KAE-393), granisetron and ondansetron were examined in the vagus nerve and cerebral cortex of rats. 5-HT and 2-methyl-5-HT induced dose-dependent depolarizations of rat isolated vagus nerve with EC50 values of 2.53 (1.

Gastric mucosal protection by YM638, a novel leukotriene D4 receptor antagonist, in rats.

YM638 ([[5-[[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl] thio]-1,3,4-thiadiazol-2-yl]thio] acetic acid) is a novel leukotriene D4 receptor antagonist. We investigated the involvement of the leukotriene D4 receptor blocking activity of YM638 in the gastric mucosal protection of this drug in rats. YM638 significantly prevented gastric lesion formation induced by water-immersion restraint stress, indomethacin, absolute ethanol, 0.

Studies on serotonin (5-HT)3-receptor antagonist effects of enantiomers of 4,5,6,7-tetrahydro-1H-benzimidazole derivatives.

We assessed the 5-HT3-receptor antagonist effects of 4,5,6,7-1H-benzimidazole compounds which are derivatives of YM060, a potent and selective 5-HT3-receptor antagonist, in isolated guinea pig colon. YM114 (KAE-393), YM-26103-2, YM-26308-2 (3 x 10(-9) to 3 x 10(-8) M) produced concentration-dependent shifts to the right of the dose-response curves for both 5-HT and 2-methyl-5-HT (2-Me-5-HT). YM114 (pA2 = 9.

Antisecretory and antiulcer effects of YM020, a new H+,K(+)-ATPase inhibitor, in rats and dogs.

We examined the effects of YM020 (3-cyanomethyl-2-methyl-8-[(3-methyl-2-butenyl)oxy]-imidazo[1,2- a]pyridine), a novel H+,K(+)-ATPase inhibitor, on gastric acid secretion and experimental gastroduodenal lesions in rats and dogs. Intraduodenal, subcutaneous and oral YM020 inhibited basal gastric acid secretion in pylorus-ligated rats with ED50 values of 9.1, 9.

YM022 [(R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl- 1H-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea], a potent and selective gastrin/cholecystokinin-B receptor antagonist, prevents gastric and duodenal lesions in rats.

We evaluated the effect of YM022 [(R)-1-[2,3-dihydro-1-(2'- methylphenacyl)-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl]-3- (3-methylphenyl)urea], a potent and selective gastrin/cholecystokinin-B receptor antagonist, on gastric acid secretion and gastric and duodenal lesions in rats. Oral YM022 (0.1-10 mumol/kg), famotidine (0.

Serotonin (5-HT)3-receptor antagonism of 4,5,6,7-tetrahydrobenzimidazole derivatives against 5-HT-induced bradycardia in anesthetized rats.

We investigated the mode of the 5-HT3-receptor antagonism of 4,5,6,7-tetrahydrobenzimidazole derivatives, YM060, YM114 (KAE-393), YM-26103-2 and YM-26308-2, against 5-HT-induced transient bradycardia in anesthetized rats. Results were compared with those of ondansetron and granisetron. YM060 (0.

Pharmacological profile of (R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo- 5-phenyl-1H-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea (YM022), a new potent and selective gastrin/cholecystokinin-B receptor antagonist, in vitro and in vivo.

(R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1,4- benzodiazepin-3-yl]-3-(3-methylphenyl)urea (YM022) is an extremely potent and highly selective gastrin/cholecystokinin (CCK)-B receptor antagonist. We compared the gastrin/CCK-B receptor-blocking properties of this compound with those of the racemate (mixture of YM022 and its S-form), its enantiomer (S-form), L-365, 260 and Cl-988 in vitro and in vivo. YM022 replaced specific binding of [125I]CCK-8 to rat brain gastrin/CCK-B receptors in a stereoselective and competitive manner.

Comparison of the effects of trimebutine and YM114 (KAE-393), a novel 5-HT3 receptor antagonist, on stress-induced defecation.

YM114 (KAE-393), (R)-5-[(2,3-dihydro-1-indolyl)carbonyl]-4,5,6,7- tetrahydro-1H-benzimidazole hydrochloride, is a derivative of YM060, a potent 5-HT3 receptor antagonist. We investigated the effects of YM114 on 5-HT3 receptors, both in vitro and in vivo, and on bowel dysfunction induced by restraint stress, 5-HT and thyrotropin-releasing hormone (TRH), and compared them with the effect of trimebutine. YM114 dose dependently inhibited the reduction in heart rate induced by 5-HT (30 micrograms/kg i.

Antisecretory effects of a novel and long-lasting histamine H2-receptor antagonist, YM-14471, in rats and dogs.

We investigated some properties of YM-14471 (2-2(-[2-(diaminomethyleneamino)thiazol-4-yl]methylthio)ethy l-5-[3- (diethylamino)propyl]-6-methyl-pyrimidine-4-one trihydrochloride), a new H2-receptor antagonist, in comparison with those of famotidine, cimetidine and omeprazole. In guinea pig atria, famotidine and cimetidine produced a competitive dose-dependent displacement of histamine-induced tachycardia. In contrast, low concentrations of YM-14471 showed competitive inhibition of tachycardia, whereas high concentrations were irreversible or slowly dissociable.

Histamine H2-receptor plays only a minor role in histamine-induced wheal response in the squirrel monkey and guinea pig.

We examined the contribution of the histamine H2-receptor to the histamine-induced wheal response in squirrel monkeys and guinea pigs. Intradermal injection of histamine, 2-pyridylethylamine (a selective H1-agonist), and dimaprit (a selective H2-agonist) dose-dependently induced the wheal response in squirrel monkeys and guinea pigs, although the reaction to dimaprit was much weaker than that to the other agonists. Chlorpheniramine dose-dependently depressed the wheal response in squirrel monkeys and guinea pigs at doses of 0.

Mechanisms of cisplatin- and m-chlorophenylbiguanide-induced emesis in ferrets.

We investigated the involvement of peripheral and central serotonin (5-HT)3 receptors in cisplatin- and 5-HT3 receptor agonist-induced emesis in ferrets. Cisplatin (10 mg/kg i.v.

Characterization of YM060, a potent and selective 5-hydroxytryptamine3 receptor antagonist, in rabbit nodose ganglion and N1E-115 neuroblastoma cells.

The 5-hydroxytryptamine (5-HT)3 receptor blocking properties of YM060, [(R)-5-[(1-methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H- benzimidazole hydrochloride], were examined by electrophysiological and radioligand binding studies. Results were compared with those for ondansetron, granisetron and the enantiomer (S-form) of YM060. 5-HT and 2-methyl-5-HT, a selective 5-HT3 receptor agonist, induced dose-dependent depolarizations of rabbit nodose ganglion with ED50 values of 24.