bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of imipramine, bupropion, chlorpromazine, and clozapine on differential‐reinforcement‐of‐low‐rate (DRL) > 72‐Sec and > 36‐sec schedules in rat
Authors: Howard James L. , Pollard Gerald T. 
Published: January 2005

AbstractThe hypothesis that a DRL schedule requiring a long pause (> 72 sec) specifically identifies antidepressant drugs was evaluated in rats pressing a lever for food reinforcement. The tricyclic antidepressant imipramine decreased responses and increased reinforcements as previously shown. However, the antipsychotics chlorpromazine and clozapine had a similar effect, as did prefeeding, and the atypical antidepressant bupropion increased responses and decreased reinforcements. Because mean baseline reinforcement rate was lower than in previous studies showing drug class specificity, the DRL requirement was reduced to > 36 sec and the drugs were tested again; effects were qualitatively similar to those in DRL > 72 in the first part of the study. The results suggest that a drug‐induced reduction in responses could account for the increase in reinforcements, that if drug class specificity exists it may occur only when baseline response and reinforcement rates are confined to a narrow range, that the failure of previous studies to show antidepressant type effects with nonantidepressants could have resulted from choice of drugs and doses, and that the type of reinforcer could be an important factor.
Geriatric psychopathology: An overview of the ailments and current therapies
Authors: Crook Thomas 
Published: January 2005

AbstractAn overview is presented of the major psychopathologic disorders in the elderly population. Alzheimer's disease and related disorders are considered, and a review is presented of the drugs currently marketed to treat these disorders and the compounds currently under investigation. Similarly, the symptoms and pharmacologic treatment of depression, anxiety, and sleep disorders in the elderly are discussed. In general, geriatric psychopharmacology is seen as a challenging and rapidly developing field of scientific inquiry.
Effects of some typical and atypical antidepressants on schedule‐controlled responding in rats
Authors: Rastogi S. K. , McMillan D. E. 
Published: January 2005

AbstractThe effects of tricylic antidepressant drugs with diverse chemical structures were studied in rats on responding maintained under a multiple fixed‐ratio (30) fixed‐interval (5 min) schedule of food resentation. Bupropion, mianserin, and nomifensine increased responding during the first half of the fixed‐interval component and during the fixed‐ratio component of the multiple schedule. Higher doses decreased rates under both the fixed‐ratio component and during the second half of the fixed‐interval component. Trazodone and trimipramine also increased rates of responding during the first half of the fixed‐interval component. Higher doses of these drugs decreased rates under the fixed‐ratio component more than the approximately equal rates during the second half of the fixed‐interval component. Iprindole, protryptyline, fluvoxamine, fluoxetine, maprotiline, clomipramine, imipramine, lithium, and chlorpromazine did not increase rates of responding under the fixed‐ratio component or under either half of the fixed‐interval component. Among these drugs, only imipramine differentially affected the nearly equal rates of responding during the second half of the fixed‐interval component and during the fixed‐ratio component. The effects of antidepressants depended on both the control rate of responding and the schedule. Rate‐increasing effects tended to be associated with antidepressants that interact with dopaminergic systems, but in general, the correlation between behavioral and biochemical effects was low.
Anticonvulsant phosphorus analogs of GABA
Authors: Cates Lindley A. 
Published: January 2005

AbstractThe dimethyl (I), diethyl (II), and di‐isopropyl (III) esters of 3‐amino‐phenylphosphonic acid and diethyl 2‐acetamidophenylphosphate (IV) were tested for inhibition of seizures induced by maximal electroshock (MES) and subcutaneous pentylenetetrazol (Metrazol) (scMet) and for neurotoxicity. Compound I was further tested for inhibition of seizures induced by subcutaneous bicuculline (scBic) and picrotoxin (scPic). Protective indices (P.I.) were compared with those reported for valproic acid (VPA) against MES and scMet and, in the case of I, with VPA, ethosuximide, trimethadione, and phenobarbital (scBic and scPic). The P.I. values of I are comparable to those of trimethadione, equal to VPA against scMet, but higher by factors of 2.6, 1.8, and 1.3 against MES, scPic and scBic, respectively.
Evidence that 5β‐progestins produce uterine relaxation by diminishing cellular calcium permeability
Authors: Kubli‐Garfias Carlos , Ortega‐Suárez Pilar , Hoyo‐Vadillo Carlos , Ponce‐Monter Héctor 
Published: January 2005

AbstractThis report presents the relaxant effect of progesterone and some of its 5β‐derivatives on the tonic contractions induced in isolated rat uterus by high K+ (40 mM) and high K+Na+‐free depolarizing solutions. Experiments were recorded with a polygraphic system. Contractions were countered by the action of progesterone (101 μM), pregnanedione (41 μM), pregnanolone (25 μM), and epipregnanolone (47 μM). The relaxant effect of progestins was, however, significantly more effective against the contraction produced by high K+ alone than that produce by high K+Na+‐free solutions. These different results suggest the ability of 5β‐reduced progesterone metabolites to block the sensitive‐to‐voltage Ca2+ channels (which are activated by K+) and also agree with the existence of a Na+/Ca2+ interchanger in the myometrial membrane. It can be concluded that 5β‐progestins induce relaxation of the uterus probably by blocking the calcium entrance into the cell.
Atherosclerosis: An overview
Authors: Comai K. , Feldman D. L. , Goldstein A. L. , Hamilton J. G. 
Published: January 2005

AbstractAtherosclerosis is a generalized disease of the arterial system that develops slowly and is symptomless until lesions have become sufficiently large and complicated to cause ischemia. The personal and economic costs of atherosclerosis are enormous. There is a consensus among experts and data from recent long‐term studies to indicate that reduction in the primary risk factors (elevated plasma cholesterol, elevated blood pressure, and smoking) leads to effective management of asymptomatic individuals at risk. Research has also led to an understanding of cholesterol metabolism and clearance pathways from some tissues. However, the factors regulating cholesterol influx and efflux from the arterial wall are currently poorly understood. The role of the monocyte/macrophage in the genesis of the atherosclerotic lesion is receiving renewed attention. The secretory products of the macrophage contain proteases and growth factors capable of causing tissue destruction and cell proliferation, two important components of advanced lesions. Recent advances in cell culture technique have allowed the in vitro growth and/or passage of all the cell types implicated in the development of the lesion. The efficacy of antiatherosclerotic agents must ultimately be proven in man. However, a battery of animal models has been developed over a period of 30 years, which when used appropriately might predict the utility of a drug in man.
Modulation of hepatic and extrahepatic LDL receptors: Involvement in the progression of atherosclerosis
Authors: Newton Roger S. 
Published: January 2005

AbstractExtensive investigation over the past 2 decades has led to a far better understanding of the role of lipoproteins in the etiology and progression of atherosclerosis. Paramount to this understanding has been the elucidation of how cells recognize these macromolecular complexes and metabolize the lipids and proteins they transport. Because of their elevation in plasma of many individuals with premature coronary heart disease, low‐density lipoproteins (LDL) have received particular attention. As primary transporters of cholesterol to cells in mammalian tissues, LDL particles are removed from blood via specific cell surface receptors that facilitate their uptake. Once internalized and exposed to lysosomal enzymes, LDL particles are degraded, “freeing” their cholesterol to regulate cellular cholesterol synthesis and modulate the number of LDL receptors on the cell membrane. This high‐affinity, high‐capacity process has been termed the LDL receptor pathway and is functional in most tissues of the body, especially in liver where over 50%percnt; of the total body LDL degradation occurs. Liver is the target organ of bile acid sequestrants (cholestyramine/colestipol) and HMG‐CoA reductase inhibitors (compactin/mevinolin), both of which induce increased expression of LDL receptors by affecting hepatic cholesterol availability. Unlike liver, the arterial wall under normal conditions is not very active at degrading LDL via the classical LDL receptor pathway. However, when hypercholesterolemia occurs, especially when there is an LDL‐receptor deficiency, the arterial wall removes 20‐‐fold more LDL than normal and with a greater fractional catabolic rate. Thus other endocytotic pathways exist by which LDL can enter cells of the arterial wall. These pathways are not as actuely regulated as the classical LDL receptor pathway, and, as a result, the arterial wall cells, particularly smooth muscle cells and resident macrophages, accumulate cholesteryl esters. In this brief review, the importance of these receptors to the etiology and progression of atherosclerosis is discussed in detail and sites of possible pharmacological intervention are identified.
CGS 10078B: A novel antihypertensive agent with multiple mechanisms
Authors: Cavaliere Thomas A. , Huebner Charles F. , Watkins Barry E. , Weiss George B. 
Published: January 2005

AbstractCGS 10078B is a potent orally effective antihypertensive agent with β‐adrenergic antagonist as well as other vasodilatory mechanisms. In spontaneously hypertensive rats, CGS 10078B (3 and 30 mg/kg, p.o.) caused rapid and significant dose‐related reductions in blood pressure that were sustained at 24 hr and accompanied by moderate reductions in heart rate. In conscious hypertensive dogs, CGS 10078B (3 mg/kg, p.o.) produced decreases in blood pressure that were of greater magnitude than those obtained with propranolol and better maintained than those obtained with nifedipine at comparable dosage. Radioligand binding assays indicated that CGS 10078B antagonizes α1‐, β1‐, and β2‐adrenoceptors and inhibits nitrendipine binding at sites associated with Ca++ channels. These biochemical results correlate well with in vitro cardiovascular studies, demonstrating that CGS 10078B possesses antagonist activity at β1‐receptors (guinea pig left atria), β2‐receptors (guinea pig trachea), β1‐receptors (rabbit aorta), and voltage‐sensitive Ca++ channels (responses to K+ or Ca++ in rabbit aorta), and on Ca++ uptake and retention (45Ca in rabbit aorta). In vivo studies with dogs treated with CGS 10078B (30 mg/kg, p.o.) also identified nonselective β‐antagonism and no interference with orthostatic reflexes. In summary, the multiple modes of action of CGS 10078B may afford a distinct clinical advantage in the treatment of hypertension.
Phencyclidine‐ type catalepsy in the pigeon: An update on chen's work
Authors: Leander J. David , Ray Wood C. , Zimmerman Dennis M. , Dykstra Linda A. 
Published: January 2005

AbstractChen [1965] described a specific form of catalepsy produced by phencyclidine and related arylcyclohexylamine analogues in pigeons. The present study expanded those observations to a variety of compounds identified as having phencyclidine‐like subjective effects in man or in drug discrimination experiments in laboratory animals. Besides phencyclidine and ketamine, etoxacrol, dexoxadrol, dextrorphan, cyclazocine, and a series of benz(f)isoquinolines produced phencyclidine‐like catalepsy, thus correlating with drug discrimination data from pigeons using phencyclidine‐like drugs. A variety of opioid agonists and mixed agonists/antagonists, along with nefopam, amantadine, baclofen, and THIP, did not produce phencyclidine‐like catalepsy. Opioid antagonists, haloperidol, and α‐methylparatyrosine did not antagonize the phencyclidine‐like catalepsy. These results emphasize the specificity of phencyclidine‐like catalepsy as a test for determining the presence or absence of phencyclidine‐like activity in compounds during drug development.
Lidamidine's effects on the lower gastrointestinal tract: A review
Authors: DiJoseph John F. , Mir G. Nabi 
Published: January 2005

AbstractLidamidine is a new, nonnarcotic, nonanticholinergic drug intended for the treatment of diarrhea. In preclinical test models, it compares favorably in both potency and duration of action with marketed antidiarrheal drugs. Lidamidine's intestinal antisecretory effects are mediated through the activation of peripheral alpha‐2 adrenoceptors. Lidamidine crosses the blood brain barrier poorly and is therefore devoid of the centrally mediated alpha‐2 effects that have limited the use of other alpha‐2 adrenoceptor agonists in the intestinal tract. Lidamidine relaxes circular and longitudinal smooth muscle in the intestinal tract and may be useful for treatment of certain intestinal motility disorders. In clinical trials, lidamidine has proven to be effective for the management of diarrheal diseases.
The effect of piroxicam on locomotor activity in rats with adjuvant‐induced arthritis
Authors: Seymour Patricia A. , Larson David L. , Browne Ronald G. 
Published: January 2005

AbstractTo evaluate the effectiveness of piroxicam, a clinically effective, long‐acting, nonsteroidal antiinflammatory drug, in a potential animal model of chronic nociception, the locomotor activity of arthritic rats was monitored over long periods of time by computer. Rats injected with complete Freund's adjuvant (CFA) displayed locomotor deficits as measured by both horizontal and vertical activity. In experiment 1, to test the effectiveness of piroxicam therapy in severely arthritic animals, administration of piroxicam (1‐‐10 mg/kg/day) was initiated 14 days after CFA injection and activity was recorded for 5 days. It was found that a single treatment significantly increased the mobility of the arthritic animals and the 4 additional days of treatment induced continued improvement in mobility and reduction in paw swelling. In experiment 2, to assess the effect of piroxicam on the development of the immobility associated with CFA‐induced arthritis, piroxicam administration (0.3‐‐3.3 mg/kg/day) was initiated prior to CFA injection and locomotor activity was monitored for 16 days. It was demonstrated that the activity of CFA‐injected rats severely and progressively decreased and that piroxicam significantly increased the activity of the arthritic rats, while having no effect on the activity of the nonarthritic control animals. These studies demonstrate the efficacy of piroxicam in arthritic rats and, although further investigation is necessary, demonstrate that the measurement of locomotor activity in arthritic rodents may be an important tool for the identification and evaluation of antiinflammatory/analgetic agents.
Species and vascular bed responses of veins and arteries to endothelial‐derived relaxing factor in dog and pig
Authors: Greenberg Stan , Diecke Friederich P. J. , Tanaka Toshio P. 
Published: January 2005

AbstractThe vascular endothelium is a source of a mediator of vascular smooth muscle (VSM) relaxation known as endothelial‐derived relaxing factor (EDRF). Endothelial‐dependent relaxation is dependent on the type of vessel under study (artery vs. vein) and on the vascular site from which the blood of vessels are derived. EDRF is released by bradykinin, adenosine, and adenosine triphosphate, substance P, serotonin, arachidonic acid, thrombin, and other relaxant substances. EDRF appears to be a labile substance with a six‐second half‐life that contains a labile ketone or carbonyl moiety in its active site. EDRF appears to be selectively inhibited by ouabain, pyruvate, and metabolic inhibitors and inactivated by potassium and sodium borohydride. EDRF appears to act by stimulating an increase in cyclic GMP in the smooth muscle cells of porcine tissues and possibly by other mechanisms in canine tissues. Canine veins possess receptors for porcine aortic EDRF but may not make EDRF itself or may have a different endothelial‐derived substance than canine arteries. Little is known concerning the factors that release or affect the action of EDRF, its mechanism of action or its chemical composition, especially in the pulmonary vasculature. The differences between release of EDRF from artery and vein and the responses to, and composition of, EDRF in vein and artery remain an area for further research.
Radioimmunoassay procedures for astemizole and metabolites in plasma
Authors: Woestenborghs Robert , Geuens Ivo , Michiels Marcel , Hendriks Rik , Heykants Jozef 
Published: January 2005

AbstractA sensitive radioimmunoassay is described for the determination of astemizole in human plasma. Immunization of rabbits with an astemizole hapten, conjugated with bovine serum albumin, resulted in the production of antiserum, capable of detecting less than 0.05 ng/ml of astemizole. Because of the cross‐reactivity of the antibodies with structurally related metabolites, plasma samples had to be submitted to two distinct extraction procedures prior to radioimmunoassay. The most selective procedure enabled the measurement of unchanged astemizole as confirmed by high‐performance liquid chromatography. The other extraction procedure allowed the determination of the fraction astemizole plus hydroxylated metabolites, which consisted mainly of astemizole and its major metabolite desmethylastemizole.
Drug‐receptor dissociation time, new tool for drug research: Receptor binding affinity and drug‐receptor dissociation profiles of serotonin‐S2, Dopamine‐D2, histamine‐H1 antagonists, and opiates
Authors: Leysen Josée E. , Gommeren Walter 
Published: January 2005

AbstractA new filter technique for in vitro measurement of the drug‐receptor dissocation time of unlabeled compounds was applied. The receptor binding affinity and drug‐receptor dissociation profiles were obtained for new and reference compounds belonging to the classes of serotonin‐S2, dopamine‐D2, and histamine‐H1 antagonists and of opiates. In vitro binding to the serotonin‐S2, dopamine‐D2, histamine‐H1, adrenergic‐α1 and ‐α2, cholinergic muscarinic and μ‐opiate receptors was studied. The binding affinity profiles provide indications about the specificity of the drugs; in each pharmacological class more selective drugs were found, whereas others cross‐reacted with various receptor sites. The drug‐receptor dissociation profiles revealed substantial differences amongst drugs in drug‐receptor dissociation times. For a particular receptor, drugs showed differences in dissociation time from half‐times of less than 1 min (e.g., alfentanil from opiate receptors) to several hours (e.g., lofentanil). In addition, drugs were found that dissociated very slowly from one receptor site and very rapidly from another receptor site (e.g., ritanserin: slow from serotonin‐S2, rapid from dopamine‐D2; spiperone: slow from dopamine‐D2, rapid from serotonin‐S2; astemizole: slow from histamine‐H1, rapid from serotonin‐S2 and adrenergic‐α1). Nevertheless, apparent binding affinities of these drugs for the receptor sites respectively were often found to be similar. Information on the drug‐receptor dissociation time allows re‐evaluation of apparent binding affinity data and gives better insight into the specificity of action of drugs. It can be applied at various levels of drug research: e.g., for interpretation of receptor binding data, drug effects on receptor regulation, functional effects of drugs, antagonizability of drug effects, and factors contributing to the in vivo duration of action of drugs. Finally, the information on drug‐receptor dissociation time may be an important factor for drug design and receptor modeling.
Conformational analysis of ketanserin
Authors: Tollenaere Jan P. , Moereels Henri , van Loon Marleen 
Published: January 2005

AbstractAn overview of the molecular modelling package Aid In Interactive Drug Analysis (AIDA) is presented. The current conformational analysis capability of AIDA is illustrated with an indepth study of the three‐dimensional characteristics of the selective S2‐receptor antagonist ketanserin. Both X‐ray crystallographic and NMR data are discussed in the light of the calculated conformational space involving three torsional angles. A procedure using AIDA to handle and inspect tens of thousands of conformations is described. On the basis of the conformational analysis the receptor‐preferred conformation of ketanserin is proposed.
Novel approaches to the pharmacotherapy of schizophrenia
Authors: Meltzer Herbert Y. 
Published: January 2005

AbstractNumerous attempts to extend the pharmacotherapy of schizophrenia beyond conventional neuroleptics are reviewed. Clozapine and melperone are atypical neuroleptics that produce few extrapyramidal side effects during acute usage and possible less tradive dyskinesia with prolonged use. Decreasing dopamingeric activity with a tyrosine hydroxylase inhibitor or dopamine autoreceptor agonists may also be of value. Neuroleptics that block voltage‐sensitive calcium channels or calcium channel blockers per se have been advocated for treatment of negative symptoms or the deficit state. Among other possible clinical approaches reviewed are: beta adrenergic blockers, clonidine, tryptophan, 5‐hydroxytryptophan, fenfluramine, GABA drugs, including high dose benzodiazepines, lithium, carbamazepine, opioid agonists and antagonists, gamma‐endorphins, TRH analogs and vasopressin. Most studies indicate these agents produce inconsistent or slight‐to‐modest benefits, either in comparison with standard neuroleptic drugs or inaddition to neuroleptics, in groups of schizophrenic patients, including some double blind placebo‐controlled trials. Those individuals who do respond sometimes, but not always, fail to relapse when the experimental drug is discontinued or fail to respond to it in subsequent trials. Consistent with the presumed heterogeneity of schizophrenia, there is some evidence supporing non‐neuroleptic drug treatment for specific schizophrenic subtypes. The various stages of this usually life‐long disorder, together with the possible mutability of the underlying etiological factors over time, requires the utmost care in clinical trials.
Tardive dyskinesias and drugs
Authors: Kane John M. , Woerner Margaret , Lieberman Jeffrey A. , Kinon Bruce J. 
Published: January 2005

AbstractAlthough considerable controversy remains as to the etiology and pathophysiology of tardive dyskinesia, epidemiologic evidence is compelling in supporting the role of neuroleptics as a major factor in the development of this syndrome. Current evidence suggests that tardive dyskinesia is a heterogeneous condition in terms of nature of onset, phenomenology, course, and response to specific treatments or pharmacologic probes. The point prevalence of tardive dyskinesia varies widely depending on the nature of the patient population and the criterion utilized to identify a “case.” The incidence of tardive dyskine‐sia among relatively young patients of varying diagnoses exposed to neuroleptics appears to be approximately 3–4% per year of cumulative neuroleptic exposure, at least for the first 6 years of such treatment. Age, vulnerability to acute extrapyramidal side effects, and a diagnosis of affective illness appear to be associated with increased risk of tardive dyskinesia development. There is clearly a need to take this aspect into consideration for new drug developments.