摘要:

AbstractThis paper reviews the screening studies carried out in India to identify Indian medicinal plants bearing anticancer and antiviral activities. The highlights of the active constituents isolated are described and, based on analysis of screening data, some correlation has been derived on the presence of anticancer and antiviral activities in the taxa belonging to different families.

ISSN:0272-4391    

DOI:10.1002/ddr.430190102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractA recently described social interaction (SI) model which is sensitive to single doses of benzodiazepines and novel non‐sedative anxiolytic agents has been used. Activities of drugs were compared in both an anxious (animals housed in pairs, tested with a novel partner) and a non‐anxious (animals housed in pairs, tested with the cage mate) condition. Diazepam displays a typical anxiolytic response, increasing SI in the anxious but not in the non‐anxious condition. This was associated with a decrease in aggression (AGG) and in locomotion (LOCO) at higher doses. Seven agents were tested which are thought to enhance central nervous system γ‐aminobutyric acid (GABA)‐mediated neurotransmission by increasing the activity of a receptor‐coupled chloride ionophore system as a major component of their action. Tracazolate, RL348, methaqualone, etomidate, LY81067, and pentobarbitone all significantly increased SI in the anxious but not the non‐anxious condition. In the anxious condition tracazolate and RL348 reduced AGG and all of these compounds except LY81067 reduced LOCO. Methaqualone and etomidate also reduced LOCO in the non‐anxious condition. In addition, an agent which reduces GABA function (picrotoxin) significantly reduced SI in already‐anxious animals, consistent with its known anxiogenic properties. Picrotoxin also reduced LOCO in both conditions. Phenobarbitone induced a non‐specific effect on SI (increased SI in both anxious and non‐anxious conditions), as well as reducing AGG in the anxious condition and LOCO in both conditions. These data suggest that agents enhancing GABA receptor‐coupled chloride ionophore function possess anxiolytic properties which may be att

ISSN:0272-4391    

DOI:10.1002/ddr.430190103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractS‐8666, a newly developed antihypertensive uricosuric diuretic, possesses an asymmetric carbon and exists as a racemic mixture. The enantioselectivity of S‐8666 in natriuresis and the renal excretory mechanisms of the S‐8666 enantiomers were examined. Dose‐dependent natriuresis of the S‐(−)‐enantiomer was observed in male Sprague‐Dawley rats (3–100 mg/kg, p.o.), female Slc:ddy mice (3–300 mg/kg, p.o.) and male NIBS Japan white rabbits (1–10 mg/kg, i.v.). The R‐(+)‐enantiomer produced no significant change in sodium excretion within dose ranges of 100–200 mg/kg p.o. for rats, 3–300 mg/kg p.o. for mice, and 10 mg/kg i.v. for rabits. The (−)‐enantiomer and racemic S‐8666 showed a high‐ceiling property like that of furosemide and unlike that of trichlormethiazide. Plasma protein binding of S‐8666 was over 95% in rabbits and 73% in beagle dogs. In rabbits, both enantiomers of S‐8666 were secreted equally from the proximal tubule; however, only the (−)‐enantiomer of S‐8666 showed diuresis in a stop‐flow pattern. In beagle dogs, secretion of racemic S‐8666 occurred from the proximal tubule and could be inhibited by probenecid. The renal excretion of S‐8666 was largely the result of tubular excretion in rabbits whereas in beagle dogs, some glomerular filtration was also involved in urinary excretion. In conclusion, S‐8666 shows enantioselectivity in natriuresis. Both enantiomers of S‐8666 are excreted mostly by the organic acid transport system in the proximal tubule, but only the (−)‐enantiomer of S

ISSN:0272-4391    

DOI:10.1002/ddr.430190104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractThe novel anxiolytic buspirone has weak or inconsistent activity in most of the animal models commonly used to identify anxiolytics. Among the six published studies of the effects of buspirone on punished level‐pressing in the rat, only one reported a clear effect (at two doses), and the peak effect was half that of diazepam. In the present study, in which rats responded for food in Geller‐Seifter conflict procedure with incremental shock, five factors were examined for influence on the effects of buspirone upon punished lever‐pressing: (1) fixed‐ratio 10 vs. fixed ratio 1 in the punishment portion of the multiple schedule, (2) drug‐naive vs. drug‐experienced rats, (3) albino vs. hooded rats, (4) SC vs. PO injection, and (5) time course up to 2 hr. The benzodiazepine chlordiazepoxide robustly increased responding punished by foot‐shock, but under none of the conditions did buspirone produce more than a small, inconsistent increase. Punished level‐pressing in the rat appears not to be an adequate method for identifying buspirone

ISSN:0272-4391    

DOI:10.1002/ddr.430190105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractDrugs known to interact with sigma receptors were studied for their effects on food and/or water intake, since the putative sigma receptor agonist N‐allylnormetazocine (NANM) has been reported to both increase and decrease food intake under various conditions. Previous investigators have shown that each enantiomer of racemic NANM [(±)‐NANM] is pharmacologically active. (+)‐NANM appears to interact preferentially with sigma receptors, and (−)‐NANM with both mu and kappa opiate receptor sites. In the present study, the effects of subcutaneously administered (±)‐NANM, (+)‐NANM, and (−)‐NANM on food intake in 20 hr food‐deprived male rats were examined. (±)‐NANM and (−)‐NANM decreased food intake stimulated by food deprivation, while (+)‐NANM exhibited no significant effect. Similarly, both (±)‐NANM and (−)‐NANM decreased water intake in 24 hr water‐deprived rats. (+)‐NANM decreased water intake in doses which may have caused disorientation. Locomotor activity was stimulated by intraperitoneal injection of 10 mg/kg of (+)‐NANM but not by the same dose of (−)‐NANM. The effects of (+)‐NANM and (−)‐NANM on food and water intake paralleled those of narcotic antagonists and did not seem related to an interaction with sigma receptors. (±)‐BMY14802 is a sigma receptor antagonist with potential antipsychotic properties. When administered to female rats by daily injection for 28 days, it did not affect weight gain except at the highest dose, 30 mg/kg. Weight gain of animals given a 30 mg/kg dose was significantly greater compared to controls. However, rats treated orally with a similar dose of (±)‐BMY14802 incorporated into the diet daily for 8 weeks did not exhibit significant weight gain compared to controls. The data argue against a significant role for sigma receptors in mediating ingestive behavior. Should sigma antagonist drugs reach the market, they may be less lik

ISSN:0272-4391    

DOI:10.1002/ddr.430190106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractIndoramin is a selective α1receptor antagonist, with pharmacologic activity similar to prazosin. However, indoramin differs from prazosin in that indoramin has membrane stabilizing activity; does not cause reflex tachycardia, first dose syncope, or orthostatic hypotension; and requires several days for onset of its antihypertensive action. Thus, indoramin may lower blood pressure independent of arterial or venous α1adrenoceptor blockade. This study compares the relative arterial and venous α1adrenoceptor blocking activity of indoramin and prazosin, followingintraduodenal(id) administration, in the canine hindpaw preparation perfused at constant flow, to their blood pressure lowering activity. Indoramin (5 and 20 mg/kg, id) inhibited the arterial and venous pressor responses to sympathetic nerve stimulation (SNS) and norepinephrine (NE). No significant differences in the magnitude of arterial and venous blockade existed. Blockade of α1adrenoceptors was maximal at 5 mg/kg of indormin. In contrast, 20 mg/kg of indoramin lowered mean arterial blood pressure (MAP) but did not affect paw perfusion pressure (PP). Prazosin (0.25 and 1.0 mg/kg, id) produced both dose‐related α1adrenoceptor blockade and reduction of MAP. Prazosin was more effective as an inhibitor of venous vs. arterial responses to SNS, and produced a different profile of inhibition of SNS than indoramin. Thus, indoramin differs from prazosin as an inhibitor of α1adrenoceptors of the canine paw. Since indoramin does not lower MAP in doses which block α1adrenoceptors of the paw and does not lower PP in the decentralized paw in doses which lower MAP, we conclude that indoramin acutely lowers MAP in the dog by a mechanism unrelated to postsynaptic α1receptor blockade, and may inhibit a subtype of α1adrenoceptor different from that inhibited b

ISSN:0272-4391    

DOI:10.1002/ddr.430190107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractCultured vascular smooth muscle and endothelial cells may be useful models for studying the cardiovascular adenosine transport system and metabolism. We have quantified the nucleoside transporter elements of cultured primate vascular smooth muscle, bovine aortic endothelial, and human umbilical vein endothelial cells by radioligand binding and by using membrane preparations of these cells and the nucleoside transporter probe nitrobenzylthioinosine ([3H]NBMPR), a potent and tightly bound inhibitor of nucleoside transport. The binding was rapid, reversible, saturable, and site‐specific. Scatchard analysis of the saturation data showed that [3H]NBMPR bound to high and low affinity binding sites in human umbilical vein endothelial cell membranes with apparent binding affinities (KD) of 0.093±0.01 nM 1.92±0.1 nM, and binding site densities (Bmax values) of 13.48±1.2 and 69+5.3 fmol/mg protein, respectively. In contrast, the binding to primate vascular smooth muscle and bovine aortic endothelial cell membranes occurred to an apparently high affinity single class of binding sites at which the KDwas 1.4±0.3nM and 0.28±0.05nM, respectively, and which had Bmax values of 1,977±163 and 1,284±267 fmol/mg protein, respectively. Scatchard analysis of the binding inhibition by dipyridamole showed a mixed type inhibition, while NBMPR inhibited the binding competitively. Several recognized nucleoside transport inhibitors and vasodilators inhibited the binding with an order of potency similar to that observed for the inhibition of [3H]NBMPR binding to guinea pig cardiac m

ISSN:0272-4391    

DOI:10.1002/ddr.430190108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractNicorandil, a new antianginal drug, exerts a coronary vasodilation effect by mechanisms different from either nitrates or slow‐channel Ca++entry blockers. This agent has been demonstrated to increase membrane K+conductance, elevate cyclic guanosine monophosphate (GMP) content, and depress Ca++current kinetics in vascular smooth muscle cells. In the myocardium, however, the direct effects of the agent have not been elucidated. We examined whether or not nicorandil could antagonize myocardial injury in the Langendorff‐perfused chick heart induced by the Ca++paradox. The Ca++paradox was produced by 15 min of Ca++‐free perfusion, followed by 10 min of Ca++reperfusion. Nicorandil was added to the perfusing solution only during the Ca++reperfusion phase. In the Ca++paradox hearts, the following were observed: (1) depression of myocardial creatine phosphokinase and adenosine triphosphate (ATP) contents; (2) elevations of myocardial H2O, Na+, and Ca++contents; and (3) ultrastructural derangement, which included contraction bands, interstitial edema, and mitochondrial swelling. Nicorandil treatment significantly attenuated the histological perturbation and part of the biochemical alterations. The present study suggests that nicorandil partially protects the myocardium against the Ca++paradox‐induced

ISSN:0272-4391    

DOI:10.1002/ddr.430190109

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractThe new xanthine derivative propentofylline (3‐methyl‐1‐[5′‐oxohexyl]‐7‐propylxanthine), administered intraperitoneally in a dose of 25 mg/kg 10 min before ligation of the left cerebral carotid artery in “sensitive” gerbils, improves the mean stroke index significantly at 4 and 24 hr postadministration. At a dose of 10 mg/kg, propentofylline improves the mean stroke index at all examined times (4, 24, and 72 hr), but at 5 mg/kg, a protective effect was obtained only after 24 hr. The mortality rate was lower in all propentofylline groups than in the control group. These results suggest that propentofylline is worth further study as a possible

ISSN:0272-4391    

DOI:10.1002/ddr.430190110

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

ISSN:0272-4391    

DOI:10.1002/ddr.430190111

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY