bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic treatment with an acetylcholine synthesis precursor, alpha‐glycerylphosphorylcholine, alters brain parameters linked to cholinergic transmission and passive avoidance behavior
Authors: Govoni Stefano , Lopez Clara M. , Battaini Fiorenzo , Trabucchi Marco 
Published: January 2005

AbstractThe present study extends previous observations on the acuta treatment with alpha‐glycerylphosphorylcholine (GPC), a putative acetylcholine (ACh) precursor, and investigates the effect of chronic treatment with this drug on scopolamine‐induced amnesia and on ACh release in the rat. The drug acutely administered antagonizes the amnesic effect of scopolamine (0.75 mg/kg s.c.) in passive avoidance experiments. The effect peaked at 600 mg/kg i.g. and lasted up to 30 hr. Potassium‐stimulated release of ACh from slices of hippocampus and cerebral cortex was measured after various doses of GPC. The dose curve study indicated that GPC was able to increase ACh release in the hippocampus already at the dose of 75 mg/kg i.g. The maximum effect was obtained with 300 mg/kg i.g. (147% of the control values). The increase of the ACh release reached a maximum 3 hrfollowing the administration, then declined toward control values. In the cortex, the effect was much less pronounced and shorter than in the hippocampus. The repeated (100 and 300 mg/kg i.g.; 22 days) GPC administration effectively antagonized scopolamine‐induced amnesia, indicating that there was no tolerance to this effect of GPC. While both doses were behaviorally active only 300 mg/kg was able to increase ACh release from hippocampus ( + 271 %) and cortex ( + 57%). The data support the hypothesis that GPC improves behavioral performance in passive avoidance through an action on cholinergic transmission. On the other hand, it should be stressed that the action on ACh release is observed in a narrow time window in contrast to the long lasting effect on behavior. It is tempting to speculate that the effect on ACh may be related to cortical activation and important but not sufficient to explain the antagonism of scopolamine‐induced amnesia. Along this line other mechanisms, possibly triggered by the action on ACh, may contribute to mediate the behavioral effect of GPC. © 1992 Wiley‐Liss, Inc.
Long‐term choline alfoscerate treatment counteracts age‐dependent structural changes in the rat hippocampus
Authors: Bronzetti Elena , Collier Wade L. , Felici Laura , Zaccheo Damiano , Amenta Francesco 
Published: January 2005

AbstractLong‐term choline alfoscerate (αGFC) treatment counteracts age‐dependent structural changes in the hippocampus of Sprague‐Dawley rats. Animals treated with a daily dose of 100 mg/kg αGFC from 18 to 24 months of age had more cells in the CA‐1 to CA‐3 fields and in the dentate gyrus compared to age‐matched cohorts. The density of silver‐gold stained fibers within the stratum oriens of the CA‐1 to CA‐2 fields was greater in rats treated with αGFC than in age‐matched controls. The ramifications of these findings are discussed. © 1992 Wiley‐Liss, Inc.
Vascular effects of class III antiarrhythmic agents
Authors: Baskin Elizabeth , Serik Carolann , Wallace Audrey , Jurkiewicz Nancy , Winquist Raymond , Lynch Joseph J. 
Published: January 2005

AbstractMethanesulfonanilide Class III antiarrhythmic agents have been shown to block a specific outward delayed rectifier K+ current, Ikr in cardiac cells. K+ conductance also is recognized to be an important regular of contractile tone in vascular smooth muscle. The purpose of the present investigation was to assess the effects of the new and potent methanesulfoanilide Class III agents E‐4031, UK‐68,798, UK‐66,914 and the Class III standard d‐sotalol in vitro in phasically active and electrically quiescent vascular smooth muscle preparations. All four Class III agents augmented phasic contractile tension in spontaneously active rat portal veins at concentrations similar to those effecting significant Class III electrophysiologic activity in cardiac muscle, but failed to contract electrically quiescent rabbit aortic rings. At concentrations exceeding effective cardiac Class III electrophysiologic concentrations, E‐4031 relaxed methoxamine‐ and histamine‐contracted rabbit aortic rings, and d‐sotalol relaxed methoxamine‐contracted aortic rings. UK‐68,798 and UK‐66,914 failed to relax spasmogen‐contracted aortic rings. The similarity in effective concentrations required for the four Class III agents to augment phasic contractile tension in the rat portal vein and increase myocardial refractoriness in cardiac muscle is consistent with the presence of similar K+ channel subtypes in the two tissues. Alternatively, the observed activities in the two tissues may be due to actions of these four Class III agents on another, non‐Ikr ion channel present in rat portal vein, with an order of potency for blockade similar to block of Ikr in cardiac tissue. © 1992 wiley‐Liss, Inc.
Binding studies with the 5‐HT1B receptor agonist [3H]CP‐96,501 in brain tissues
Authors: Lebel Lorraine A. , Koe B. Kenneth 
Published: January 2005

AbstractBinding studies in rat brain membranes have shown that [3H]CP‐96,501 is a selective, high affinity radioligand for 5‐HT1B receptors. Additional studies with [3H]CP‐96,501 in brain tissues of several other species were undertaken to investigate its utility in detecting this receptor subtype. The presence of 5‐HT1B receptors in brain membranes of the hamster and gerbil was demonstrated with [3H]CP‐96,501. This finding was confirmed by [3H]5‐HT binding experiments that also indicated the presence of other 5‐HT1 subtypes (possibly 5‐HT1D, 5‐HT1E) in these species as well as the rat. Negligible specific binding of [3H]CP‐96,501 was found in membranes of guinea pig brain, dog hypothalamus, bovine caudate, pig choroid plexus, and several human brain tissues, consistent with the reported absence of the 5‐HT1B receptor subtype in these species. Autoradiographic examination of rat brain sections labeled by [3H]CP‐96,501 showed a dense localization in areas known to be enriched in 5‐HT1B receptors (e.g., globus pallidus, substantia nigra, superior colliculus, subiculum). On the other hand, brain sections of dog and guinea pig appeared to show no specific binding of [3H]CP‐96,501 by autoradiography, in agreement with the lack of brain 5‐HT1B receptors in these tissues. © 1992 Wiley‐Liss, Inc.
Cortical focal stroke model to evaluate neuroprotective action of drugs
Authors: Mahadik Sahebarao P. , Wakade Chandramohan G. 
Published: January 2005

AbstractThe experimental central nervous system (CNS) stroke model of cerebral cortical focal isch‐ emia in the rat is detailed to produce consistent and reproducible ischemic injuries, and is discussed for its adequacy to investigate the molecular mechanisms of ischemic injuries and to evaluate the neuroprotective efficacy of drugs. The model involves the permanent occlusion of ipsilateral (left) common carotid artery (CCAo) and middle cerebral artery (MCAod), and 1 hr occlusion of contralateral (right) CCAo. It is relatively easy to perform, highly reproducible, and does not result in mortality, and therefore is most suitable to delineate the time‐dependent changes in biochemical processes associated with various CNS injuries to anatomically distinct regions of the brain initiated after ischemia. These injuries include primary and peri‐ischemic injuries due to direct interruption of blood supply, and secondary non‐ischemic injuries in brain areas with intact blood circulation. The consistency, reproducibility, and reliability are based on the analyses of several physiological (tissue levels of edema, Na+, K+, and Ca++) and biochemical (membrane levels of fatty acids, [Na+ + K+]‐ATPases, Ca++‐ATPase, and levels of enzymes of oxy‐radical metabolism) indices of plasma membrane dysfunction which paralleled the functional deficits. These characteristics of the model make it possible for us to investigate the temporal relationship of a cascade of these acute physiological and biochemical processes in addition to loss of energy and nutrition, alterations in membrane lipid metabolism, increased lipid peroxidation, and alterations in receptor‐mediated transfer of information. These processes, if not attenuated in time, can lead to cellular death. Since the ischemic injury affects several neurotransmitter systems simultaneously in anatomically distinct areas of the brain, probably through generalized alterations of cellular plasma membrane physicochemical properties, the MCAo model is also well suited to compare efficacy of drugs with a wide range of physiological actions using a large number of the same biochemical and behavioral param‐ eters. In summary, a highly reproducible and consistent MCAo model of ischemia is adequate, if not identical to human ischemic stroke, to study several relevant variables of human stroke which include transient ischemia, reperfusion, different degree of ischemia due to varying lengths of occlusion or site of occlusion, hemorrhage, hypoglycemia, and hypothermia, and to evaluate the efficacy of a drug to stop the most acute injury process(es) before injury reaches the “point of no return.” © 1992 Wiley‐Liss, Inc.
Psychopharmacological profile of a new chroman derivative with 5‐hydroxytryptamine1A agonist properties: S 20499 (+)
Authors: Porsolt Roger D. , Lenègre Antoine , Caignard Daniel H. , Pfeiffer Bruno , Mocaër Elisabeth , Guardiola‐Lemaître Beatrice 
Published: January 2005

AbstractS 20499 is the (+) enantiomer of the racemic compound S 20244 (4‐N‐(methoxychromane‐3‐yl) N‐propylamino butyl‐8‐azaspiro 4,5 decane‐7,9 dione), a novel 5‐hydroxytryptamine1A (5‐HT1A) agonist. The present experiments examined the potential anxiolytic and 5‐HT1A agonist activity of S 20499 (+) in behavioral experiments in rodents. Tests used were the lrwin, activity meter, and tail suspension tests in mice and the Vogel conflict, forepaw treading, and lower lip retraction tests in rats. Further tests examined its duration of activity and the effects of chronic treatment. In most experiments, its effects were compared with the (−) enantiomer (S 20500). Neither S 20499 (+) nor S 20500 (−) was lethal in mice up to 256 mg/kg. S 20499 (+) induced signs of sedation (hypoactivity, decreased traction and muscle tone, ptosis, and hypothermia) in the lrwin test in the dose range 4–64 mg/kg i.p. and a dose‐dependent decrease in locomotion (activity meter) from 2 mg/kg. At high doses (128–256 mg/kg) S 20500 (−) had qualitatively different effects, inducing signs of excitation and stereotyped behavior. At lower doses (16–64 mg/kg), its effects were similar to those of S 20499 (+) but it was between two‐ and fourfold less potent. S 20499 (+) increased the duration of immobility in the tail suspension test (anxiolytic/tranquilizing activity) from 16 mg/kg, whereas S 20500 (−) had no effects up to 32 mg/kg. BothS 20499 (+) and S 20500 (−) increased the number of shocks taken in the Vogel conflict test (anxiolytic activity) at 4 and 16 mgikg, respectively. The duration of activity of S 20499 (+) was between 2 and 4 hr and its effects were maintained after chronic administration over 5 days. Finally, both enantiomers induced forepaw treading and lower lip retraction in rats (signs of 5‐HT, agonist activity), with S 20499 (+) being at least four times as potent as S 20500 (−). Taken together, the results are consistent with other available data suggesting potential anxiolytic activity for S 20499 (+), probably arising through its agonist activity at central 5‐HT1A, receptors. © 1992 Wiley‐Liss, Inc.
Effects of the complexation of various fentanyl analogs in hydroxypropyl‐β‐cyclodextrin after epidural and intrathecal administration in rats
Authors: Meert Theo F. , Putteman Peter , Peeters Jef 
Published: January 2005

AbstractComplexation of various equipotent doses of fentanyl‐like opioids in hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) results in a potentiation of the spinal activity of these opioids after both epidural and intrathecal administration in a fixed diluent volume of 10 μl. The first active and mot optimal concentrations of HP‐β‐CD after epidural administration differed between the opioids and varied from 1 to 20% HP‐β‐CD. The duration of deep surgical analgesia increased at optimal concentrations of HP‐β‐CD with a factor 3 for fentanyl (15% HP‐β‐CD), 3.6 for sufentanil (5–10% HP‐β‐CD), respectively. Increasing the concentrations of HP‐β‐CD above these optimal concentrations did not further potentiate the analgesic activity of the opioids. The complexation of the opioids in HP‐β‐CD also increased the duration of supraspinal side‐effects. However, except for lofentanil, the potentiations of the analgesic activity were always longer lasting than those for the secondary side‐effects. As a consequence, there was a gain in the total time of analgesia without side‐effects. After intrathecal administration, there was no gain in the duration of deep surgical analgesia after complexation of fentanyl, carfentanil and alfentanil in HP‐β‐CD. For both sufentanil and lofentanil, maximal potentiation of analgesia was measured at 10% HP‐β‐CD with, respectively, 2.8‐ and 1.7‐fold increases in the duration of analgesia. Also intrathecally, there was some gain in the duration of duration of analgesia without supraspinal side‐effects. These results on the potentiation of the opoids with HP‐β‐CD are discussed in relation to the lipophilicity of the tested opioids. © 1993 Wiley‐Liss, Inc.
Potent 5‐hydroxytryptamine3 receptor antagonist activity of RG 12915
Authors: Martin Gregory E. , Chase Billee J. , Davis Marjorie A. , Pendley Charles E. 
Published: January 2005

AbstractRG 12915, N‐(1‐azabicyclo[2.2.2.]octan‐3(S)‐yl)‐2‐chloro‐(5aS, 9aS)‐5a,6,7,8,9,9a‐hexahydrodibenzofuran‐4‐carboxamide, a potent antiemetic agent active in reducing emesis produced by antieoplastic agents, was examined in tests of 5‐hydroxytryptamine3 (5‐HT3) receptor blockade. RG 12915 was found to be a potent antagonist of 5‐HT3 receptor activation both in blocking 5‐HT‐induced contractions of guinea‐pig ileum and in blocking the Bezold‐Jarisch effect in the rat. Compared to several other 5‐HT3 antagonists, RG 12915 had a greater pA2 value (11.2) for blocking 5‐HT‐induced contractions of guinea pig ileum than zacopride (8.3); BRL 43694 (granisetron) (9.1); and GR 38032F (ondansetron) (7.4). Falls in heart rate due to 5‐HT3 receptor activation following intravenous (i.v.) administration of 5‐HT (the Bezold‐Jarisch effect) were also potently reduced by RG 12915. Minimum effective dose (MED) levels (in parentheses), defined as the lowest dose at which each compound produced a significant reduction in the Bezold‐Jarisch effect, were determined for RG 12915 (1.0μg/kg, i.v.); zacopride (3.0); granisetron (9.0); and ondansetron (27.0). The order of potency in blocking 5‐HT3 receptor activation was generally the same as the order of potency in 5‐HT3 receptor binding. RG 12915 had a lower Ki value (0.17±0.02 nM, mean ± SEM) in binding studies using 3H‐GR‐65630 as the ligand in rat entorhinal cortex tissue than either zacopride (1.5±0.4); granisetron (1.7±0.3); or ondansetron (6.2±2.1). RG 12915 was also found active in blocking contractions of guinea pig ileum and the Bezold‐Jarisch effect induced by the somewhat selective 5‐HT3 receptor agonist 2‐methyl‐secrotonin. The results support the idea that this orally active antiemetic agent is a potent antagonist of 5HT3 receptor activation. © 1993 Wiley‐Liss, Inc.
Effects of intracerebroventricular administration of ethylcholine aziridinium ion on hippocampal cholinergic system, assayed in vivo by a brain dialysis technique, and on spatial memory of rats
Authors: Tajima Toshihisa , Yoshimine Noboru , Goto Tsutomu , Ikari Hiroyuki , Kuzuya Fumio , Endo Hidetoshi 
Published: January 2005

AbstractWe attempted to clarify the effect of hippocampal function on the spatial memory of rats by creating a lesion in the hippocampus with ethylcholine aziridinium ion (AF64A). The hippocampus was damaged by injecting AF64A into the lateral ventricles, 3 nmol/3 μl per side. At 1 or 4 weeks after the injection, acetylcholine (ACh) was measured in perfusion samples collected via brain dialysis of the hippocampus of freely moving rats. The release of ACh stimulated by scopolamine was reduced at 1 week but not at 4 weeks post‐injection. A behavioral change on the eight‐arm radial maze test was also observed in the acquisition or retention trials to determine the deficit in spatial memory, whether acquisition or retention. In the acquisition trial, the initial correct response was decreased and the total error count was increased at 1.5 to 2.5 weeks, but not at 3 weeks, after the AF64A injection. However, those indices remained unchanged in the retention trial. These observations suggest that the hippocampus may be required for the acquisition of spatial memory, but that the stored memory, but the stored memory is located outside the hippocampus, the hippocampus is not concerned with the retrieval process, or the retrieval process may be hippocampal but not cholinergic. The hippocampal cholinergic system would be concerned with the acquisition of spatial memory. Thus, AF64A‐treated rats may serve a model for hippocampal cholinergic dysfunction and the recovery from hippocampal cholinergic damage. © 1993 Wiley‐Liss, Inc.
Adenosine A1 receptor and ligand molecular modeling
Authors: Dudley Mark W. , Peet Norton P. , Demeter David A. , Weintraub Herschel J. R. , Ijzerman Ad P. , Nordvall Gunnar , van Galen Philip J. M. , Jacobson Kenneth A. 
Published: January 2005

AbstractThis symposium provided a forum for presentations by the relevant groups on ligand design and ligand binding on the adenosine A1 receptor. Agreement appears to exist that the “N6C8” model of ligand binding to the receptor is the preferred mode. A consensus has not yet been reached on the actual placement of the ligand in the receptor and the exact amino acids which interact in its binding. Two viable models exist at present. Both can be tested with selective site‐directed mutagenic studies on the A1 receptor as well as with additional designed ligands. © 1993 Wiley‐Liss, Inc.
P2 receptor: Subclassification and structure‐activity relationships
Authors: Cusack Noel J. 
Published: January 2005

AbstractStructure‐activity relationships (SAR) at P2 receptors that support their subclassification into at least five nucleotide receptor subtypes, P2Z, P2T, P2Y, P2U, and P2X, are reviewed. The P2Z receptor is the most sensitive to alterations to ATP. The adenine base, D‐ribose sugar, and 5′‐triphosphate chain are absolute requirements, but substitutions are tolerated at the C‐2 position and replacement by sulphur of an ionized phosphate oxygen leads to enhanced potency. The P2T receptor, where ADP is the only endogenous agonist, has an absolute requirement for the adenine base, D‐ribose sugar, and a 5′‐diphosphate chain. C‐2 substitution and replacement by sulphur of an ionized oxygen is tolerated. Many analogs of AMP and of ATP are antagonists. The P2Y receptor requires an adenine base, D‐ribose, and a 5′‐polyphosphate for maximal potency only. C‐2 substitution, and replacement of an ionized oxygen by sulphur, can enhance potency. Methylenephosphonate potencies depend on the position of the methylene group. ADP‐β‐F is a specific agonist. The P2X receptor is least sensitive to alterations to ATP. There is no requirement for and adenine base, D‐ribose sugar, or triphosphate chain. Methylenephosphonates and some phosphorothioates have enhanced potencies. L‐AMP‐PCP is a specific agonist. Evidence from SAR for a P2U subtype is reviewed. SAR studies are complicated by the presence of ectonucleotidases. The overall subclassification of P2 receptors is inadequate and awaits the availability of selective competitive antagonists. © 1993 Wiley‐Liss, Inc.
Anticancer activities of adenine nucleotides in tumor bearing hosts
Authors: Rapaport Eliezer 
Published: January 2005

AbstractThe utilization of adenosine 5′‐triphosphate (ATP) infusions against solid refractory cancers is based on the preclinical findings that low levels of extracellular ATP significantly inhibit the growth of a variety of human and murine tumor cells. The mechanisms of tumor cell killing by extracellular ATP are attributed to effects mediated by its interaction with P2 purine receptors as well as non‐receptor‐mediated pore formation in the tumor cell membrane. The achievement of elevated extracellular blood plasma pools of ATP is accomplished by the administration of adenine nucleotides which yield elevated liver, red blood cell, and plasma compartment pools of ATP. Administration of AMP or ATP to tumor‐bearing murine hosts produced, in addition to the cytotoxic effects against the tumor, a variety of host mediated anticancer activities, including significant inhibition of host weight loss in cachectic tumor models. The inhibition of several adverse events Which are among the hallmarks of cancer cachexia is the result of prevention of the significant depletion of visceral energy stores in cachectic animals after the administration of adenine nucleotides, leading to the successful maintenance of hepatic functions, the resumption of normal protein synthesis in the liver, and inhibition of the synthesis of hepatic acute‐phase proteins. Thus, the administration of ATP as an anticancer agent in humans at levels (below 0.1 mg/kg min) which do not adversely affect systemic and cardiovascular functions is expected to lead to the following activities resulting from the generation of elevated hepatic, red blood cell, and blood plasma ATP pools: cytolytic effects against the tumor, inhibition of host weight loss, and other adverse effects of cachexia, anti‐pain effects, modulation of blood flow to the tumor, positive effects on motor functions and performance status due to increases in several other parameters which are also known to be affected by elevated red blood cell and blood plasma (extracellular) ATP levels. © 1993 Wiley‐Liss, Inc.
Cardiovascular effects of adenosine and the adenosine A1 Receptor antagonist NPC 205 are altered with age in guinea pigs
Authors: de Garavilla Lawrence , Valentine Heather L. , Schenden Jan S. , Kinnier William J. , Hanson Robert C. 
Published: January 2005

AbstractResponsiveness of the cardiovascular system to the effects of vasoactive agents can vary with age. The endogenous metabolite adenosine has negative chronotropic, inotropic, and hypotensive effects. The purpose of this study was to determine if the effects of exogenously administered adenosine and the adenosine A1 receptor antagonist 1,3‐di‐n‐propyl‐8‐(hydroxyphenyl) xanthine (NPC 205) vary with age. The effects of adenosine on mean arterial blood pressure (MABP), heart rate, and cardiac contractility (LV dP/dt) were investigated in two groups of guinea pigs: a young group (3–4 weeks) and an older group (72–75 weeks). In vivo, the older animals were shown to be significantly more sensitive to the negative inotropic, chronotropic, and hypotensive effects of adenosine, whereas the responses to R‐N6‐phenylisopropyladenosine (R‐PIA), a metabolically stable analog of adenosine, were similar in both age groups. In vitro, right atria from young (3–4 weeks) and old (72–75 weeks) guinea pigs exhibited no age‐related differences in the sensitivity to the negative chronotropic effects of adenosine or R‐PIA. Younger animals were more sensitive to the positive inotropic effects of the adenosine A1 receptor antagonist, NPC 205. In addition, basal heart rates were significantly lower in the older group of animals. It may therefore be concluded that there age‐related effects of adenosine. Furthermore, comparison of the effects of adenosine to the effects of the stable analog R‐PIA and the adenosine antagonist NPC 205 suggests that these differences may be due to changes in adenosine metabolism with age. © Wiley‐Liss, Inc.