bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alfentanil infusions for peroperative and postoperative analgesia
Authors: Noorduin Henk , Waldron Heather , van Peer Achiel , Vanden Bussche Gabriel 
Published: January 2005

AbstractThe theoretical and clinical data available to date on the use of alfentanil by infusion as a supplement to N2O anaesthesia are summarized. These data suggest that alfentanil plasma levels of 200–400 ng/ml are required to provide adequate peroperative analgesia, depending upon the severity of the surgical procedure. Patients may be expected to awaken and breathe spontaneously at plasma levels of less than 200 ng/ml. Infusion regimens that achieve the required plasma levels without prolonging recovery are recommended for both minor and major surgery. Tentative suggestions are also given for the use of alfentanil by infusion in the postoperative period in spontaneously breathing patients.
R 58 735: A new antihypoxic drug with anticonvulsant properties and possible effects on cognitive functions
Authors: Wauquier Albert , Clincke Gilbert , Ashton David , De Ryck Marc , Fransen Joannes , van Clemen Gust 
Published: January 2005

AbstractR 58 735, a benzthiazole derivative, is a potent antihypoxic agent with anticonvulsant properties. As an antihypoxic drug, it was more potent than any other reference substance in hypobaric hypoxia in mice and in histotoxic dysoxia and nitrogen hypoxia in rats. In the nitrogen hypoxia test, R 58 735 was equipotent in males and females, and the p.o.\i.v. ratio varied from 2.8 to 2.6. The antihypoxic activity of orally administered R 58 735 latested more than 8, but less than 24 hr. The anticonvulsant profile of R 58 735 resembled that of flunarizine, i.e., blockade of the tonic convulsions induced by pentylenetetrazol, allylglycine, or bicuculline, but not of clonic convulsions, except those seen in audiogenic seizureprone mice. In the allylglycine or bicuculline tests, it was more potent than any other reference anticonvulsant. In the bicuculline test, there were no sex‐related differences in activity, and the p.o.\s.c. activity ratio was 2.01 in males and 1.74 in females. Following oral administration, the duration of anticonvulsant activity in the bicuculline test was more than 8, but less than 24 hr. In guinea pigs, R 58 735 completely antagonized hypoxia‐induced amnesia at a dose of 2.5 mg\kg s.c. Furthermore, it enhanced acquisition of a two‐way avoidance task over a broad dose range (0.63–20 mg\kg) in rats.
R 58 735, a novel antihypoxic drug improves memory in rats
Authors: Clincke Gilbert , Sahgal Arjun 
Published: January 2005

AbstractRats weren given free choice to enter either a black or a white compartment when placed on an illuminated runway. On the fourth day a mild shock was given upon entry. Animals were subsequently injected with either solvent or a dose of R 58 735. Drug treatment dose‐relatedly increased entry latency on retention test (day 5) and doubled choice reversal at the highest dose (25 mg\kg s.c.) given. The results suggest that R 58 735 has a direct, memory enhancing action.
Interactions of haloperidol with discriminative responding controlled by 10 mg/kg of cocaine in rats
Authors: Colpaert Francis C. 
Published: January 2005

AbstractNine rats were trained to discriminate 10 mg/kg of cocaine HCI from saline in a two‐lever food‐reinforced drug discrimination procedure. Saline and 0.31–10 mg/kg doses of cocaine were tested for generalization after pretreatment with either vehicle or 0.04 and 0.16 mg/kg of haloperidol. The 0.04 and 0.16 mg/kg doses of haloperidol produced a 2.3 and 5.0‐fold shift to the right, respectively, of the cocaine generalization gradient. Extrapolation of the generalization data suggests that about 3 mg/kg of haloperidol is required to antagonize completely the discriminative effects of the 10 mg/kg training dose of cocaine. Cocaine (0.63 mg/kg) reversed the rate‐depressant effects of 0.04 mg/kg of haloperidol, but even 10 mg/kg only partially attenuated the behavioral depression produced by 0.16 mg/kg of haloperidol. Also, up to 10 mg/kg doses of cocaine exerted no reliable effect on the alternative lever responding produced by 0.04 or 0.16 mg/kg of haloperidol. The data suggest that 2.3–5.0‐fold shift of the cocaine gradient, but not a complete blockade of the discriminative effects of the 10 mg/kg training dose of cocaine, can be achieved with doses of haloperidol at which the drug presumably interacts in a specific manner with dopamine receptors in the brain.
Short‐term and chronic effects of transdermal nitroglycerin in stable angina pectoris
Authors: Hunter Kenneth W. , Mahapatra Rajat 
Published: January 2005

AbstractThirty‐five patients with stable angina pectoris (AHA functional class II or III) entered a 5‐week short‐term study to determine the efficacy and safety of a transdermal therapeutic system of nitroglycerin (TDN; 5 to 20 mg/day). Nineteen of these patients were available for a final reassessment in a long‐term follow‐up after at least 1 year of continuous therapy; hence, total treatment time exceeded 8,400 patient‐days. The therapeutic efficacy of TDN was determined from weekly patient diaries of angina frequency, as well as the clinical assessment of functional class according to the criteria of the American Heart Association. Frequency of angina was reduced from ten to less than three attacks per week in all treatment groups, irrespective of angina severity at the outset, and reduction in anginal frequency was statistically significant (P <0.05) in the 10‐, 15‐, and 20‐mg dosage groups. Sixteen of the 19 patients (84%) who entered the long‐term follow‐up required no change in dosage, and all 19 patients showed improvement in AHA function class at the final reassessment. Our study showed that TDN exerted a sustained, clinically significant therapeutic benefit during both a short‐term study and long‐term follow‐up in patients with stable angina pectoris.
Pinacidil monohydrate—a novel vasodilator: Review of preclinical pharmacology and mechanism of action
Authors: Cohen Marlene L. 
Published: January 2005

AbstractPinacidil dose‐dependently decreased blood pressure in normotensive, renal hypertensive, spontaneously hypertensive, and neurogenic hypertensive rats; in anesthetized cats; and in normotensive and renal hypertensive dogs by a mechanism associated with decreased total peripheral resistance and reflex tachycardia. Pinacidil was 2–4‐fold more potent as an antihypertensive than hydralazine. Antihypertensive activity of pinacidil was not modified by α, β, cholinergic, or histaminergic receptor antagonists and was not associated with calcium channel blockade, activation of cyclooxygenase, or formation of the vasodilator, adenosine. In vitro, pinacidil relaxed blood vessels contracted with several agonists by a mechanism that was independent of an intact endothelium, did not increase either CAMP or cGMP, and was approximately 700 times more potent than minoxidil or hydralazine. Thus, pinacidil is a direct‐acting vasodilator, whereas minoxidil and hydralazine must be metabolized to a vasoactive species or exert some indirect effect for anithypertensive activity in vivo. Pinacidil lowered blood pressure in decerebrated cats, and only trace amounts of radiolabeled pinacidil distributed to the brain, suggesting minimal central effects. Pinacidil was rapidly absorbed after oral administration in rats, dogs, and man, showing a plasma half‐life of approximately 30 min in all three species with peak plasma levels within 30 to 60 min. The major biotransformation product of pinacidil in rats, dogs, and man was pinacidil‐N‐oxide; and renal excretion was the main elimination pathway for both agents. Pinacidil‐N‐oxide was less potent than pinacidil as an antihypertensive agent and showed approximately 10–100‐fold less vasodilation than pinacidil in vitro. In summary, pinacidil is a clinically effective novel antihypertensive agent that nonselectively inhibits contractile responses of arterial and other smooth muscle.
The effects of clovoxamine on sleep of normal volunteers: A double‐blind placebo‐controlled study
Authors: Wilson William H. , Ban Thomas , Coleman Bernard , Vause Beth , Papadatos John 
Published: January 2005

AbstractIn a double‐blind placebo‐controlled study the effects of clovoxamine on sleep were evaluated. Each of 12 healthy male volunteers was given clovoxamine (50 and 150 mg) and placebo according to a repeated‐measures randomized Latin square design. All night sleep EEGs and subjective evaluations of sleep were recorded on each night. Clovoxamine was found to have effects on sleep EEG and subjective evaluation that were consistent with findings reported for other antidepressants such as imipramine.
Dimaprit stimulation of gastric acid secretion in rhesus monkeys and dogs
Authors: Russell James , Becci Michels , Mir G. Nabi 
Published: January 2005

AbstractTests were performed to characterize the gastric secretory effect of the H2 agonist, dimaprit, in rhesus monkeys. Dose‐response studies were performed. The monkeys were chaired, and increasing doses of dimaprit (0.03 to 3.0 mg/kg hr) were infused intravenously. Gastric secretions were collected continuously through a nasogastric tube and were measured at 15‐min intervals. The completeness of collection was confirmed based on the recovery of an intragastric marker. Dimaprit dose dependently increased the total acid output (ED50 = 0.198 mg/kg hr) and the volume of gastric secretion. Ranitidine (1 mg/kg hr, i.v.) shifted the dimaprit dose‐response curve to the right in a parallel fashion causing a 13‐fold increase in the ED50 for acid output (2.54 mg/kg hr). Similarly, ranitidine competitively inhibited the secretory effect of dimaprit in the gastric fistula dog. In addition, when a single dose of dimaprit was infused over a 4‐hr period, both the monkey and dog exhibited a secretory plateau followed by a secretory “fade.” We conclude that the secretory effects of dimaprit are qualitatively similiar for rhesus monkeys and dogs.
Effects of flunarizine on rat cerebral cortex
Authors: Reid Kennet H. , Marrannes Roger , Wauquier Albert 
Published: January 2005

AbstractFlunarizine was tested using a single dose (40 mg/kg IP) and multiple doses (30 mg/kg PO presurgery) in 200–250 g male Wistar rats, using physiological measures related to the rapid ionic shift seen in cerebral cortex following a sudden insult. The threshold for initiation of a spreading depression was increased by flunarizine treatment only in rats in which the cortex had previously been injured. The time to rapid ionic shift after cardiac arrest (global ischemia) was increased by both flunarizine and phenytoin. Other measures tested showed no difference in normal cortex under flunarizine treatment. Flunarizine appears to have little or no effect on normal cortical tissure, but rather seems to exert a therapeutic effect on injured cortical tissue. Flunarizine may be a useful agent in the management of cerebral trauma.
Proof of antihypoxidotic properties of tenilsetam in man by EEG and psychometric analyses under an experimental hypoxic hypoxidosis
Authors: Saletu B. , Grünberger J. , Anderer P. 
Published: January 2005

AbstractProof of the protective properties against cerebral hypoxic hypoxidosis of a new potentially nootropic drug, tenilsetam (TEN), were studied as compared with 5 mg co‐dergocrine mesylate (CDM) in a double‐blnd, placebo‐controlled trial. Hypoxic hypoxidosis was induced by a fixed gas combination of 9.8% oxygen and 90.2% N2, equivalent to 6,000 m altitude, which was inhaled for 23 min under normobaric conditions by 15 healthy volunteers. They received randomized after an adapation session placebo, 150 mg, 300 mg, and 900 mg TEN and 5 mg CDM. Blood gases, quantitative EEG, and psychometric measures were obtained under normoxic (21% O2) and hypoxic (9.8% O2) conditions before as well as 2,4,6, and 8 hr after oral drug administration. Blood gas analysis demonstrated under hypoxia a drop in PO2 from 91 to 37 mm Hg and in PCO2 from 38 to 33 mm Hg, while pH increased from 7.41 to 7.47. Under these hypoxic conditions, computer‐assisted spectral analysis of the EEG showed an increase of delta/theta, decrease of alpha, and increase of superimposed fast beta activity indicative of deterioration in vigilance. The latter was documented at the behavioral level by deterioration of intellectual and mnestic functions, psychomotor activity, performance in a reaction time task, mood, and wakefulness. Both TEN and CDM attenuated this brain dysfunction, although in a different manner. Whereas TEN induced an increase in alpha and decrease of fast beta activity as compared with placebo, 5 mg CDM attenuated delta/theta and increased alpha‐adjacent beta activity. Multivariate analysis based on changes in all EEG‐variables exhibited the highest dosage TEN and the reference substance significantly different from placebo. Psychometric data added—despite high variance—further evidence for antihypoxidotic/nootropic properties of both drugs, as psychometric performance under hypoxia deteriorated by 45% after placebo, while after 5 mg CDM, 150 mg, 300 mg, and 900 mg TEN only by 25, 27, 39, and 22%, respectively. Based on changes in all 12 psychometric variables obtained at all times, 900 mg, but also 150 mg TEN as well as 5 mg CDM, were significantly different from placebo. Under normoxic conditions, multivariate analyses did not show any significant differences to placebo, and only singular neurophysiological and behavioral changes were observed.
Role of GTP‐binding proteins in hormone and drug action: Adenylate cyclase and other transduction processes
Authors: Rodbell Martin 
Published: January 2005

AbstractA large number of surface membrane receptors are coupled to proteins (N or G) that bind GTP. The N proteins generally consist of three distinct subunits, designated α, β, and γ, of which only the α‐subunit binds and degrades GTP to GDP. The α subunits are homologous in structure at the GTP‐binding domains but vary in function. When activated by GTP‐γ‐S and Mg ions or by homones and GTP, α‐subunits are released from the complexes with the β/γ‐subunits remain membrane‐bound during the activation of the α‐subunits. The α‐subunits regulate adenylate cyclase; activate phospholipases that break down phosphoinositides to inositol‐trisphosphate and diacylglycerides; regulate potassium channels and voltage‐activated calcium channels; and may regulate Mg ion channels and glucose transport. Based on the varied actions of the same α‐subunit and evidence that the α‐subunits are modified by kinases and possibly other protein‐modifying enzymes, it is proposed that these GTP‐binding proteins are the primary messengers of hormone action; when released from their moorings with β/γ‐complexes (and receptors) into the cytosol the α‐proteins are suggested to regulate several signal‐amplifying processes (enzymes, channels, transporters) and are subject to alterations in structure and function. In this sense the α‐GTP‐binding programs can be considered as “programmable messengers.”
The usefulness of social behavior in behavioral pharmacology
Authors: Niesink Raymond J. M. , van Ree Jan M. 
Published: January 2005

AbstractThis paper surveys the possibility and importance of studying social behavior of rats in pharmacology. Social behavior of rats tested in dyadic encounters can be used for studying experimentally induced changes in this behavior. Different exogenous factors like administering psychopharmacological agents or changes in the test environment can easily and reproducibly affect social behavior of rats. The involvement of endogenous factors in social behavior is discussed. In this respect, especially the hormones β‐endorphin and γ‐MSH seem to act as intrinsic factors involved in the regulation of social behavior. The models described are useful tools for studying the interaction between psychopharmaca and social behavior and may be of importance for studying mechanisms underlying psychopathological disturbances in humans.
Effects of vinpocetine in scopolamine‐induced learning and memory impairments
Authors: Groó Dóra , Pálosi Éva , Szporny László 
Published: January 2005

AbstractScopolamine‐induced memory dysfunctions are related to reduced cholinergic transmission. In our experiments scopolamine (3.0 mg/kg i.p.) inhibited acquisition and induced retrograde amnesia in a one‐trial step‐ through passive avoidance task in mice. We have studied the effect of vinpocetine (CavintonR), in the amnesic states mentioned above compared to that of vincamine, nicergoline (SermionR), and papaverine, to assess its activity on learning and memory processes impaired by scopolamine. Vinpocetine decreased the disrupting effect of scopolamine on acquisition and prevented and restituted the memory loss with 21.0 and 7.0 mg/kg i.p. peak effect dose, respectively. It facilitated the recall of memory traces damaged by scopolamine. Vincamine (3.5–63.7 mg/kg i.p.) showed a favorable effect in two of the four tests (reversal of amnesia and recall). Nicergoline (5–40 mg/kg i.p.) exerted moderate activity, and papaverine (10–40 mg/kg i.p.) was ineffective in the situations tested. Our findings indicate that vinpocetine directly or indirectly influences the cholinergic system, which may explain its previously reported beneficial effect in electroconvulsive shock‐ and hypoxia‐induced experimental amnesic states, and its therapeutic activity in human mental and cognitive disorders.
Buspirone antagonizes the expression of conditioned taste aversion in rats
Authors: Ervin Gregory N. , Soroko Frank S. , Cooper Barrett R. 
Published: January 2005

AbstractWhen the parameters of taste aversion conditioning and testing have been appropriately adjusted, benzodiazepines and barbiturates will markedly antagonize the expression of moderate taste aversions in rats. We call this the taste aversion conflict model of anxiety. In the present study, we investigate whether buspirone HCl (buspirone; p.o. and i.p.) is active in the taste aversion conflict model and whether buspirone will also increase unsuppressed saccharin (SACC) intake. We also investigated the effects of imipramine, desipramine, phenelzine sulfate, chlorpromazine, scopolamine and d‐amphetamine sulfate in the taste aversion conflict model. To assess the possible effects of buspirone on the GABA‐benzodiazepine supramolecular receptor complex, we compared buspirone with certain benzodiazepines, meprobamate and sodium phenobarbital on the antagonism of pentylenetetrazol‐induced lethality in mice. Unlike benzodiazepines, meprobamate and phenobarbital, buspirone did not antagonize pentylenetetrazol‐induced lethality. However, like those other anxiolytics, buspirone markedly antagonized the expression of conditioned taste aversion. All nonanxiolytic drugs tested had either no effect or very slight effects on the expression of conditioned taste aversion. These results suggest that the taste aversion conflict model is sensitive to novel anxiolytics and that it is selective for drugs clinically effective in the treatment of generalized anxiety disorders in man.
Pharmacological profiles in vivo of benzodiazepine receptor ligands
Authors: Gardner Colin R. 
Published: January 2005

AbstractSince the discovery of specific binding sites for benzodiazepines in the brain, a range of compounds have been discovered that do not have the benzodiazepine structure but that do interact with the benzodiazepine receptors. Classical benzodiazepines were considered to be agonists at these receptors. Some compounds only possess part of the profile of classical benzodiazepines and antagonise benzodiazepines in those test procedures in which they are totally inactive. Such compounds are regarded as partial agonists. The discovery of methyl and ethyl β‐carboline‐3‐carboxylate opened a new vista in the pharmacology of benzodiazepine receptors. These agents and now several other compounds act on the benzodiazepine receptors to induce effects functionally opposite to those of classical benzodiazepines (proconvulsant and convulsant) and have been called inverse agonists. Both agonists and inverse agonists can be blocked by compounds with affinity for the receptors but little intrinsic activity (antagonists). A recent increase in the number of benzodiazepine receptor ligands with in vivo activities allows comparison of a range of compounds from several different structral groups. Their pharmacological profiles suggest that these compounds all fit onto a continuum of behavioural effects related to activation of benzodiazepine receptors.
Cyclic AMP and cyclic GMP phosphodiesterases: Target for drug development
Authors: Pang David C. 
Published: January 2005

AbstractCyclic nucleotide phosphodiesterases catalyze the hydrolysis of 3′,5′ cyclic nucleotides to the corresponding nucleoside 5′ monophosphates. Multiple forms of cyclic nucleotide phosphodiesterase have been identified in both the cardiac muscle and vascular smooth muscle from various species. These isozymes differ in apparent molecular mass, chromatographic properties, substrate specificity, immunologic reactivity, sensitivity to inhibitors, and mode of regulation. The phosphodiesterases play important roles in the regulation of cyclic nucleotide concentrations, which in turn mediate cellular responses to a variety of biological stimuli. The development of phosphodiesterase inhibitors to increase intracellular cyclic nucleotide levels represents an important pharmacological approach to the treatment of various cardiovascular diseases.
Platelet‐activating factor‐induced cellular and pathophysiological responses in the cardiovascular system
Authors: Doebber Thomas W. , Wu Margaret S. 
Published: January 2005

AbstractRecent findings in several laboratories have demonstrated the important interactions of platelet‐activating factor (PAF) with vascular endothelial cells, and thus the potential role of this lipid mediator in the pathophysiology of the cardiovascular system. PAF potently and specifically stimulates the in situ and in vivo release of tissue‐type plasminogen activator from the vascular endothelium [Emeis and Kluft, 1985]. Several lines of evidence indicate that PAF may play a critical role in the neutrophil adhesion to endothelial cells stimulated with thrombin or leukotrienes [Zimmerman et al., 1985]. PAF is a potent stimulator of Ca+2 efflux from endothelial cells, which thus might be an early step in the suspected involvement of the endothelium in in vivo responses to PAF, such as hypotension and increased vascular permeability [Brock and Gimbrone, 1986]. In our own laboratory, we have developed a specific and potent PAF receptor antagonist, L‐652,731, in order to determine the role of PAF in different animal models of disease. Utilizing this receptor antagonist as well as other criteria, PAF is indicated to be a major mediator of the endotoxin‐induced hypotension in rats and soluble immune complex‐induced hypotension and extravasation, also in rats. The immune complex‐induced increased plasma glucosaminidase is partially mediated by PAF, whereas the immediate and complete neutropenia is not indicated to involve PAF.