摘要:

AbstractMg2+and Ca2+‐channel blockers exert similar effects on the cardiovascular system. These agents have been successfully used for treating hypertension and for protecting against myocardial ischaemia. The exact mechanism of action of Ca2+‐blocking drugs, including verapamil, is unknown. It is proposed that Ca2+‐blockers stimulate the Mg2+transport system and Mg2+diffusion into the cell, thereby enhancing Mg2+influx. This, in turn, causes suppression of the slow inward Ca2+current and fast inward Na+current, resulting in decreased transport of Ca2+and Na+. Ca2+‐blockers might also influence outward K+and Mg2+currents, thereby altering the shape and duration of the action potential. Since Mg2+is involved in maintaining the structural and functional integrity of the cardiovascular system, Mg2+‐mediated mechanisms of action for Ca2+‐antagonists appe

ISSN:0272-4391    

DOI:10.1002/ddr.430130102

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

年代:1988

数据来源: WILEY

摘要:

AbstractWy 47,384 was examined in an extensive series ofin vivopreclinical behavioral tests to determine its possible efficacy and side effect liability as a novel antipsychotic agent. Wy 47,384 was found to suppress avoidance responding following both i.p. and p.o. administration at doses that did not generally impair escape performance. Wy 47,384 also was found to be considerably more potent in antagonizing climbing behavior than stereotyped behavior produced by apomorphine. However, this compound demonstrated some cataleptogenic potential in catalepsy and global behavioral assessment tests. Wy 47,384 also produced limited sedation in motor activity, conflict, and rotorod ataxia tests, but the compound did not interact with ethanol. Wy 47,384 did not demonstrate preclinical anxiolytic activity in conflict behavior tests, and it did not show antidepressant effects in tests designed to assess beta‐adrenergic sensitivity. These studies show that Wy 47,384 is a specific putative antipsychotic agent with limited extrapyramidal and sedative side effect potentia

ISSN:0272-4391    

DOI:10.1002/ddr.430130103

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

年代:1988

数据来源: WILEY

摘要:

AbstractMDL 11,939 (α‐phenyl‐1‐(2‐phenylethyl)‐4‐piperidine methanol) has been shown, throughin vitrostudies utilizing radioligand binding and isolated tissues as well as throughin vivotests of central and peripheral serotonergic activity, to be a potent, selective antagonist at 5‐hydroxytryptamine receptors of the 5‐HT2subtype. In particular, MDL 11,939 shows low affinity for the 5‐HT1and 5‐HT3subtypes of the serotonin receptor and displays low or negligible affinity for alpha adrenergic, dopaminergic, cholinergic, histamininergic, and opiate receptors. Because the 5‐HT2subtype of the serotonin receptor has been implicated in the control of both the central nervous and vascular systems of experimental animals, it is likely that a compound with the potency and specificity of MDL 11,939 has interesting

ISSN:0272-4391    

DOI:10.1002/ddr.430130104

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

年代:1988

数据来源: WILEY

摘要:

AbstractAs the potential clinical applications of LHRH agonists increase, the issue of side effects on nonreproductive organ systems assumes greater significance. LHRH agonists administered continuously or in twice‐daily injections accelerated body weight gain in female rats. Two different LHRH agonists produced similar effects on body weight in female rats. When Leuprolide (LHRHa) was given to female rats in twice‐daily injections, the adrenal weight increased after 21 days of treatment, whereas administration by osmotic minipumps produced no significant effect on adrenal weight. When another agonist, Zoladex (LHRHz), was given continuously for 52 and 229 days to female rats, the adrenal weight decreased. No change was noted in adrenal weight or body‐weight gain of male rats given LHRHz continuously for 51 and 62 days. Reproductive‐organ weights were significantly reduced in all LHRH‐agonist‐treated animals. Serum progesterone in female rats and testosterone in male rats were significantly decreased following treatment with LHRHz. No significant differences were noted in serum prolactin, growth hormone, or corticosterone. The mechanisms and significance of these findings ar

ISSN:0272-4391    

DOI:10.1002/ddr.430130105

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

年代:1988

数据来源: WILEY

摘要:

AbstractThe effects of magnesium pyrrolidone carboxylate (MAG 2) on the amnesias induced by scopolamine, diazepam, and electroconvulsive shock (ECS) were studied in a passive avoidance procedure in the mouse and compared with the effects of a standard dose of piracetam. Amnesia was induced by injecting scopolamine or diazepam (1 mg/kg intraperitoneally [i.p.]) 30 min before or ECS administered immediately after the first session (S1) of the passive avoidance task. MAG 2 was studied in a dose range of 128 to 1,024 mg/kg and compared with piracetam (2,048 mg/kg), both drugs being administered orally (p.o.) 60 min before S1. Retention was measured 24 hr later (S2) in the absence of any treatment. Further experiments investigated the effects of repeated administration of MAG 2 (twice daily for 3 days) on diazepam‐induced amnesia. Additional experiments investigated the interactions of the compound with the major behavioral effects of the amnesic treatments, namely scopolamine‐induced hyperactivity, diazepam‐induced release of punished behavior (four plates test), and ECS‐induced convulsions. MAG 2 dose‐dependently attenuated the memory deficits induced by the three amnesic treatments after acute treatment and more effectively antagonized diazepam‐induced amnesia after repeated than after acute treatment. It did not affect either scopolamine‐induced hyperactivity, diazepam‐induced release of punished behavior or ECS‐induced convulsions. These results point to the specificity of MAG 2′s antiamnesic activity and suggest that it might be a useful agent for the treatment of memory deficits of diffe

ISSN:0272-4391    

DOI:10.1002/ddr.430130106

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

年代:1988

数据来源: WILEY

摘要:

AbstractIn view of a possible beneficial action of some of the xanthine derivatives in brain ischemia or anoxia, metabolic effects of synthetic propentofylline (3‐methyl‐[5′ oxohexyl]‐7‐propyl‐xanthine) have been studied in multiple‐dose experiments with suspensions of rat brain synaptosomes incubated at various temperatures. The rate of D‐[14C] glucose conversion to14CO2was measured in the absence or in the presence of 2,4‐dinitrophenol (DNP) used to uncouple oxidative phosphorylations and thus simulate mitochondrial uncoupling accompanying neuronal damage in brain ischemia. Propentofylline suppressed synaptosomal glucose oxidations in a dose‐dependent logit‐linear manner. At 15°C, ED50concentrations (responsible for the suppression of initial oxidation rates by one half) were highest (8 × 10−3M) in the case of low‐rate oxidations in Na‐free media and were lowest (7.4 × 10−4M) in respect to the high‐rate DNP‐stimulated metabolism, which thus appeared as particularly susceptible to propentofylline. Cold‐induced modifications of the metabolic responsiveness of snaptosomes to DNP (flattening of the biphasic DNP log dose‐response profile at reduced incubation temperatures) were intensified by propentofylline, suggesting a synergism between hypothermia and the depressant action of the drug. At equal concentrations, propentofylline strongly inhibited uncoupled oxidations while theophylline remained ineffective or induced even additional stimulatory effects. This is similar to the differential in vivo effects of the two xanthines on brain metabolism and blood flow coupling and further supports the possibility of a protective energy‐sparing role of propentofylline in brain ischemia, particularly

ISSN:0272-4391    

DOI:10.1002/ddr.430130107

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

年代:1988

数据来源: WILEY

摘要:

AbstractIn the present study, cerebral energy metabolism and the alanine/glutamate ratio were evaluated in gerbils at the end of or 6, 24, or 48 hr after ischemia (10 min) induced by clamping both common carotid arteries. At the end of ischemia, the energy substrates were dramatically reduced, while lactate and pyruvate levels and the alanine/glutamate ratio were increased. During 48 hr of recirculation, the high‐energy phosphate increased but never to normal values; lactate, which is low in the early postischemic period, progressively increased; pyruvate fell but without returning to normal; the alanine/glutamate ratio decreased without reaching normal value. RU 24722 (vindeburnol) or vincamine were administered subcutaneously 15 min, 10, 24, and 34 hr after ischemia. RU 24722 completely inhibited the increase in lactate levels observed 24 and 48 hr after ischemia, improved pyruvate recovery, and normalized the alanine/glutamate ratio, but vincamine did not. Neither compound had any effect on the tissue concentrations of phosphocreatine, ATP, ADP, or AMP. The ability of RU 24722 to prevent the postischemic lactate accumulation associated with the normalization of the alanine/glutamate ratio indicates that it should improve the capacity for postischemic cerebral metabolic recovery and that it also has a different biochemical profile from that of vincamin

ISSN:0272-4391    

DOI:10.1002/ddr.430130108

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

年代:1988

数据来源: WILEY

ISSN:0272-4391    

DOI:10.1002/ddr.430130109

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

年代:1988

数据来源: WILEY

ISSN:0272-4391    

DOI:10.1002/ddr.430130101

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

年代:1988

数据来源: WILEY