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Results for “Dibenzoxazepines”

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At least 19 recordsLinked to original sources
PubMed1978

Mechanism of the cardiovascular activity of dibenzoxazepine in cats.

Small i.v. doses of dibenzoxazepine (DBO) (50--400 microgram/kg) given to anesthetized cats resulted in dose related increases in heart rate (up to 70 beats/min) and blood pressure (up to 80 mm Hg). The pressor response was blocked by pretreatment of the animals with phentolamine; pretreatment for 3 days with 6-hydroxdopamine; with mecamylamine and spinal transection between C1 and C2 but not by propranolol or adrenalectomy. The increase in heart rate was blocked by pretreatment with propranolol, 6-hydroxydopamine, mecamylamine and spinal transection whereas adrenalectomy only affected the response slightly. DBO produced only negative effects on the isolated rabbit heart. Bioassay of arterial blood showed an increased level of circulating catecholamines corresponding to the cardiovascular stimulation. DBO had no tyramine-like activity on the isolated rabbit aortic strip but slightly potentiated the contraction induced by noradrenaline. These findings strongly suggest that the cardiovascular effects resulted from central stimulation of the sympathetic nervous system. A minor part of the observed sympathomimetic effects may also be the result of the ability of DBO to potentiate the effects of noradrenaline perhaps by blocking catecholamine uptake.

Animals↗
PubMed1990

A novel dibenzoxazepine derivative (BY-1949) increases regional cerebral blood flow.

The effects of BY-1949, a novel dibenzoxazepine derivative, on the regional cerebral blood flow were investigated in conscious cats. Oral administration of BY-1949 (10-50 mg/kg) significantly increased in a dose-related manner the regional cerebral blood flow in all brain regions examined. Vinpocetine (20 mg/kg p.p.) had similar effects that were shorter-lasted than those of BY-1949. From these results, it seems likely that amelioration by BY-1949 of cognitive impairment following cerebral ischemia/hypoxia or that occurs on ageing is at least partly explainable in terms of its effects on the cerebral circulation.

Animals↗
PubMed1992

An activation of synaptosomal Na+,K(+)-ATPase by a novel dibenzoxazepine derivative (BY-1949) in the rat brain: its functional role in the neurotransmitter uptake systems.

In search of factors mitigating the final outcome of ischemic and epileptic brain damage, we tested a novel dibenzoxazepine derivative (BY-1949), as the compound has been shown to be effective under these two conditions. First, using rat brain, we assessed whether or not BY-1949 affects the Na+,K(+)-ATPase activity. Although in vitro applications of either BY-1949 or its three major metabolites did not cause any apparent effects, both acute and chronic oral administrations of the compound (10 mg/kg) invariably increased the Na+,K(+)-ATPase activity in the synaptosomal plasma membranes by increasing Vmax values. Second, it was shown by this study that the drug treatment caused marked increases in the uptake of both glutamic acid and gamma-aminobutyric acid into the synaptosomes. These results suggest that the activity against ischemic/epileptic brain damage by BY-1949 is explicable, at least partly, in terms of improvement of ionic derangements across the neural membranes via Na+,K(+)-ATPase activation.

Animals↗
PubMed1991

The role of cGMP in the anti-aggregating properties of BY-1949, a novel dibenzoxazepine derivative.

The anti-aggregatory activity of a novel agent, BY-1949, 3-methoxy-11-methyldibenz (b,f) (1,4) oxazepine-8-carboxylic acid, was examined using rabbit platelets. Oral administration of BY-1949 (10 or 30 mg/kg) inhibited platelet aggregation induced by ADP, collagen, and arachidonate in a dose-related fashion. In in vitro studies, however, neither BY-1949 nor its major metabolites inhibited platelet aggregation, even at a concentration similar to that attained in plasma in vivo. With regard to the anti-aggregatory action of BY-1949, biochemical analysis revealed that BY-1949 preferentially augmented cyclic GMP (cGMP) formation, via inhibition of phosphodiesterase activity, without altering cyclic AMP (cAMP) formation. Furthermore, the in vitro anti-aggregatory activity was significantly enhanced when the platelets were concomitantly treated with nitric oxide (NO). Based on these results, it is suggested that the in vivo anti-aggregatory effects of BY-1949 are at least partly elicited via platelet/endothelium interactions, in which cGMP plays a pivotal role.

Animals↗
PubMedDate not supplied

The lipid-lowering profile in rodents. AZ-1355, a new dibenzoxazepine derivative.

The lipid-lowering profile of ethyl 10,11-dihydro-4-methoxydibenz[b,f]-(1,4)oxazepine-8-carboxylate (AZ-1355) has been evaluated using clofibrate as a reference compound. This compound is structurally unrelated to any other hypolipidemic agent. AZ-1355 was selected not only for its effect in reducing serum lipids, but also because it inhibits platelet aggregation in vivo and elevates the prostaglandin I2/thromboxane A2 ratio in vitro. It lowers serum total cholesterol in Triton-treated hyperlipidemic mice, and also lowers serum total cholesterol and triglyceride in dietary hyperlipidemic rats. In golden hamsters chosen for further evaluation, AZ-1355 reduced serum, liver and cardiac lipids, improved the beta/alpha-lipoprotein ratio and increased the HDL cholesterol. Thus, it is apparent that the lipid-lowering profile of AZ-1355 differs from that of clofibrate.

Animals↗
PubMed1993

N-substituted dibenzoxazepines as analgesic PGE2 antagonists.

8-Chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-acetylhydrazide (1, SC-19220) has been previously reported by us and others to be a PGE2 antagonist selective for the EP1 receptor subtype with antinociceptive activities. Analogs of SC-19220, in which the acetyl moiety has been replaced with pyridylpropionyl groups and their homologs, have been synthesized as illustrated by compounds 13 and 29. These and other members of this series have been shown to be efficacious analgesics and PGE2 antagonists of the EP1 subtype. This report discusses the structure activity relationships within this series.

Analgesics↗
PubMed1979

Ultrastructure of rat lungs following exposure to aerosols of dibenzoxazepine (CR).

Three groups of 18 animals were exposed respectively to the following large doses of dibenz (b.f)-1:4 oxazepine (CR) aerosols, 78,200,140,900 and 161,300 mg/min/m3. Animals were killed at intervals from 15 min to 2 days, and the lungs examined macroscopically, by electron microscopy and conventional histology. There were no deaths during or after exposure. Macroscopically the lungs from all rats appeared normal. Microscopically there were a few areas of mild congestion, haemorrhage and emphysema, but there was little variation between the different groups. Electron micrographs revealed some morphological alteration of the epithelium and endothelium but only occasional changes in the interstitium. The alterations took the form of "ballooning" of the endothelium with isolated foci of swelling and thickening of the epithelium. Interstitial oedema was observed in one animal only which was exposed to the highest concentration. The effects appeared similar in all groups, and are thought to be transient. The results of this investigation suggest that even high doses of CR aerosols cause minimal damage to the lung, and the structural alterations which do occur are believed to be due to the stress to which the animals were subjected during the exposure period.

Aerosols↗