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Results for “Cinanserin”

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At least 19 recordsLinked to original sources

PubMed1995

Protective effect of the serotonin receptor antagonist cinanserin in two canine models of pacing-induced myocardial ischemia.

Previous studies have indicated that structurally dissimilar serotonin2 (5HT2) antagonists can protect globally ischemic/reperfused reperfused rat hearts. We therefore determined if the 5HT2 antagonist cinanserin can protect the ischemic myocardium in two models of pacing-induced ischemia in anesthetized dogs. In one model, dogs were subjected to repeated 5-min episodes of pacing superimposed upon left anterior descending coronary artery stenosis such that an ST segment elevation of 10-11 mV was obtained and upon cessation of pacing, a return of ST segment elevation to baseline. In vehicle-treated animals, this ST segment elevation to baseline. In vehicle-treated animals, this ST segment elevation was constant for all pacing-induced ischemic episodes. After infusion of 20 micrograms/kg/min cinanserin (intracoronary, i.c.), ST segment elevation was significantly reduced during pacing-induced ischemia at all times measured postdrug. In the second model, animals were subjected to pacing-induced ischemia for 15 min such that segmental shortening was reduced to zero. Upon cessation of pacing-induced ischemia, recovery of shortening was assessed. In vehicle-treated dogs, function recovered to only 40% of baseline at 3 h into recovery. Pretreatment with 5 micrograms/kg/min cinanserin i.c. significantly improved recovery of postischemic function. In both protocols, cinanserin had no effect on ischemic regional blood flow or peripheral hemodynamics. Thus, cinanserin appears to exert profound protective effects in two models of effort-induced ischemia.

Analysis of Variance↗

PubMed2005

Cinanserin is an inhibitor of the 3C-like proteinase of severe acute respiratory syndrome coronavirus and strongly reduces virus replication in vitro.

The 3C-like proteinase (3CLpro) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is one of the most promising targets for anti-SARS-CoV drugs due to its crucial role in the viral life cycle. In this study, a database containing structural information of more than 8,000 existing drugs was virtually screened by a docking approach to identify potential binding molecules of SARS-CoV 3CLpro. As a target for screening, both a homology model and the crystallographic structure of the binding pocket of the enzyme were used. Cinanserin (SQ 10,643), a well-characterized serotonin antagonist that has undergone preliminary clinical testing in humans in the 1960s, showed a high score in the screening and was chosen for further experimental evaluation. Binding of both cinanserin and its hydrochloride to bacterially expressed 3CLpro of SARS-CoV and the related human coronavirus 229E (HCoV-229E) was demonstrated by surface plasmon resonance technology. The catalytic activity of both enzymes was inhibited with 50% inhibitory concentration (IC50) values of 5 microM, as tested with a fluorogenic substrate. The antiviral activity of cinanserin was further evaluated in tissue culture assays, namely, a replicon system based on HCoV-229E and quantitative test assays with infectious SARS-CoV and HCoV-229E. All assays revealed a strong inhibition of coronavirus replication at nontoxic drug concentrations. The level of virus RNA and infectious particles was reduced by up to 4 log units, with IC50 values ranging from 19 to 34 microM. These findings demonstrate that the old drug cinanserin is an inhibitor of SARS-CoV replication, acting most likely via inhibition of the 3CL proteinase.

Animals↗

PubMed1977

Morphine and ethanol as discriminative stimuli: absence of antagonism by p-chlorophenylalanine methyl ester, cinanserin, or BC-105.

It is well established that the effects of morphine and ethanol can function as discriminative stimuli in the rat. The present investigation sought to determine whether discriminated responding mediated by morphine and ethanol is affected by (a) p-chlorophenylalanine methyl ester (p-CPA) an inhibitor of the synthesis of 5-hydroxytryptamine (5-HT) and (b) antagonists of 5-HT. The blocking agents employed were cinanserin, in ethanol-trained subjects, and BC-105, in morphine-trained subjects. No evidence of antagonism was obtained with either BC-105 or cinanserin. Results with p-CPA were somewhat variable but no consistent or statistically significant reduction in the efficacy of morphine or ethanol as discriminative stimuli was observed. The present results with p-CPA are at variance with earlier work by Schechter (1973) and by Rosecrans et al. (1973) who observed antagonism of the stimulus effects of ethanol and morphine, respectively, following depletion of 5-HT with p-chlorophenylalanine.

Animals↗

PubMed1988

Tonic immobility and the serotonergic system in chickens: differential blockade of receptors by cyproheptadine and cinanserin.

Low doses of serotonin potentiated immobility durations in 2 1/2-week-old chickens (Gallus gallus) while high doses attenuated the response. Cyproheptadine, a serotonergic antagonist, eliminated increases generated by low doses of serotonin and reduced durations in control subjects, but had no effect on the attenuation produced by high doses of the drug. Cinanserin, another serotonergic blocker, also eliminated the potentiation generated by low doses of serotonin and partially reduced the attenuation caused by high doses, but had no effect on immobility durations in control animals. Larger doses of cinanserin eliminated the attenuation produced by high doses of serotonin and increased durations in control subjects. Results are discussed in terms of the differential blockade of various serotonin receptors.

Animals↗

PubMed1976