Search results for "Azepines"
showing 10 items of 135 documents
A novel cyclo-oxygenase-2 inhibitor modulates catabolic and antiinflammatory mediators in osteoarthritis.
2004
ITB (6-(p-bromophenyl)amino-7-(p-chlorophenyl)indazolo[2',3':1,5]-1,2,4-triazolo[4,3-a]-1,3,5-benzotriazepine) is a novel inhibitor of cyclo-oxygenase-2 (COX-2) with antiinflammatory activity in animal models. In the present study, we investigated the effect of this compound on the production of catabolic or antiinflammatory mediators in osteoarthritis (OA) cartilage. In OA cartilage explants, ITB inhibited the production of prostaglandin E(2) (PGE(2)), tumour necrosis factor-alpha (TNF-alpha) and matrix metalloproteinase-13 (MMP-13) in a concentration-dependent manner, whereas nitrite was partially reduced. On the contrary, ITB increased the production of interleukin (IL)-10 and the expres…
Modification of depressant and disinhibitory action of flurazepam during short term treatment in the rat
1972
Employing a fixed-interval schedule of reinforcement (temporal discrimination), alternated punished (fixed-ratio) and unpunished (variable-ratio) schedules of reinforcement, a Conditioned Avoidance Response, and studying its interaction with Pentobarbital on general anaesthesia, it has been shown that flurazepam hydrochloride after a single treatment induces very intense depressant effects and slight disinhibitory effects. Short term treatment at longer than daily intervals reduces the depressant effect and unmasks the disinhibitory effect. The phenomenon is probably caused by selective tolerance concerning the depressant action. The results are discussed from the point of view of the signi…
Enantioselective syntheses of dopaminergic (R)- and (S)-benzyltetrahydroisoquinolines.
2001
Optically pure (1S,R)- and (1R,S)-benzyltetrahydroisoquinolines (BTHIQs), 12a,b as the major diastereomers, were prepared by stereoselective reduction of the isoquinolinium salt possessing (R)- and (S)-phenylglycinol as the chiral auxiliary, respectively. The absolute configurations of (1S,R)-13a hydrochloride (O-debenzoylated derivative from 12a) and (1R,S)-12b diastereomers were unambiguously determined by single-crystal X-ray analysis. Reductive removal of the chiral auxiliary group, subsequent N-propylation, and cleavage of the methylenedioxy group furnished the optically active catecholamines (1S)-16a and (1R)-16b in good overall yield. We have separately prepared for the first time pa…
Staphylococcal α-toxin provokes coronary vasoconstriction and loss in myocardial contractility in perfused rat hearts: Role of thromboxane generation
2000
Background —Cardiac performance is severely depressed in septic shock. Endotoxin has been implicated as the causative agent in Gram-negative sepsis, but similar abnormalities are encountered in Gram-positive sepsis. We investigated the influence of the major exotoxin of Staphylococcus aureus, staphylococcal α-toxin, in isolated perfused rat hearts. Methods and Results —α-Toxin 0.25 to 1 μg/mL caused a dose-dependent increase in coronary perfusion pressure that more than doubled. In parallel, we noted a decrease in left ventricular developed pressure and the maximum rate of left ventricular pressure rise (dP/dt max ), dropping to a minimum of <60% of control. These changes were accompani…
Repression of the nuclear receptor small heterodimer partner by steatotic drugs and in advanced nonalcoholic fatty liver disease.
2015
The small heterodimer partner (SHP) (NR0B2) is an atypical nuclear receptor that lacks a DNA-binding domain. It interacts with and inhibits many transcription factors, affecting key metabolic processes, including bile acid, cholesterol, fatty acid, and drug metabolism. Our aim was to determine the influence of steatotic drugs and nonalcoholic fatty liver disease (NAFLD) on SHP expression and investigate the potential mechanisms. SHP was found to be repressed by steatotic drugs (valproate, doxycycline, tetracycline, and cyclosporin A) in cultured hepatic cells and the livers of different animal models of NAFLD: iatrogenic (tetracycline-treated rats), genetic (glycine N-methyltransferase-defi…
Furosemide action on cerebellar GABA(A) receptors in alcohol-sensitive ANT rats.
1999
Furosemide increases the basal tert-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding and reverses the inhibition of the binding by gamma-aminobutyric acid (GABA) in the cerebellar GABA(A) receptors containing the alpha6 and beta2/beta3 subunits. These effects are less pronounced in the alcohol-sensitive (ANT) than in the alcohol-insensitive (AT) rat line. The difference between the rat lines in the increase of basal [35S]TBPS binding was removed after a longer preincubation with ethylendiaminetetraacetic acid (EDTA) containing buffer, but long preincubation did not reduce the GABA content of the incubation fluid or remove the difference in GABA antagonism by furosemide. The GABA sensi…
Sex differences in escape-avoidance response in mice after acute administration of raclopride, clozapine, and SCH 23390.
1998
Sex differences in the effects of haloperidol in the escape-avoidance response in mice have previously been found in various studies carried out in our laboratory. Males were more affected than females by the disruptive effects of this neuroleptic. The work described herein extended the study of these sex differences to raclopride, clozapine, and SCH 23390, using several doses of each drug in acute administration. The results showed dose-dependent sex differences in the deteriorating effects of these dopamine antagonists in the escape-avoidance response. Male mice were more affected by the inhibitory effects of these drugs, showing fewer escape responses and more nonresponses than females. …
Effect of verapamil and diltiazem on isolated gastro-oesophageal sphincter of the rat
1985
Abstract The effect of verapamil and diltiazem on the contraction induced by agonists on the rat lower oesophageal sphincter in-vitro has been studied. Both calcium entry blockers inhibited the contractile response to acetylcholine, carbachol and KCl. The potency of the inhibitory action was diltiazem &gt; verapamil. The results give substance to the use of calcium entry blockers in the treatment of oesophageal spasm.
Sensitization to the rewarding effects of morphine depends on dopamine
2005
The influence of dopamine (DA) on sensitization to the rewarding effects of morphine was evaluated. The effects of pre-treatment with saline or morphine plus naloxone, CGS 10746B, haloperidol, SCH 23390 and raclopride, on the place conditioning induced by 2 mg/kg morphine were evaluated. This dose was ineffective in saline pre-treated animals but induced a clear conditioned place preference in mice pre-treated with morphine, CGS 10746B or haloperidol. Conversely, animals pre-treated with morphine plus naloxone, CGS 10746B, SCH 23390, raclopride and the high dose of haloperidol did not acquire place preference. Our results demonstrated that DA release and subsequent DA D1 and D2 receptor act…
Role of dopamine neurotransmission in the long-term effects of repeated social defeat on the conditioned rewarding effects of cocaine
2016
Numerous studies report that social defeat stress alters dopamine (DA) neurotransmission in several areas of the brain. Alterations of the mesolimbic dopaminergic pathway are believed to be responsible for the increased vulnerability to drug use observed as a result of social stress. In the present study, we evaluated the influence of DA receptors on the long-term effect of repeated social defeat (RSD) on the conditioned rewarding and reinstating effects of cocaine. For this purpose, the D1R antagonist SCH 23390 and the D1R antagonist raclopride were administered 30 min before each social defeat and a cocaine-induced CPP procedure was initiated three weeks later. The expression of the D1R a…