bluuebunny/crossref_metadata_2025_split huggingface dataset:
NPC 205 is a potent and selective adenosine A1, receptor antagonist: Correlation among receptor binding, biochemical, and physiological assays
Authors: Kaplita P. V. , Abreu M. E. , Connor J. R. , Erickson R. H. , Ferkany J. W. , Hicks R. P. , Schenden J. A. , Noronha‐Blob L. , Hanson R. C. 
Published: January 2005

AbstractThe chemical synthesis of 8‐aryl‐1,3‐dialkyl derivatives of xanthine and the ability of these compounds to interact with adenosine A1 and A2 receptors in vitro (in receptor binding, biochemical, and physiological assays) are described. NPC 205 (1,3‐dipropyl‐8‐[4‐hydroxy‐ phenyl]xanthine) was the most potent and A1‐selective antagonist of the series. NPC 205 was twice as potent at PACPX (1,3‐dipropyl‐8‐[2‐amino‐4‐chlorophenyl]xanthine) and at least 20‐fold more potent than 8‐phenyltheophylline to inhibit specific binding of [3H]‐cy‐clohexyladenosine to guinea pig and rat brain membranes. Along with NPC 189 (1,3‐dimethyl‐8‐[4‐hydroxyphenyl]xanthine), NPC 200 (1,3‐dipropyl‐8‐phenylxanthine), and PACPX, NPC 205 also was a more potent antagonist of A1‐receptor‐mediated inhibition of adenylate cyclase (AC) in rat cortex than A2 receptor‐coupled stimulation of AC in PC‐12 cell membranes. NPC 205 was, in fact, 30‐fold more potent and fourfold more selective than PACPX for the AC‐coupled A1 receptor function and exhibited competitive interactions with A1 receptors. In isolated guinea pig atria, NPC 205, NPC 189, NPC 200, and PACPX all reversed 5′N‐ethyl‐carboxamidoadenosine (NECA)‐induced depression of tension and rate. In the Langendorff isolated perfused guinea pig heart preparation, NPC 205 was more potent than PACPX in reversing NECA‐mediated depression in developed tension and rate (A1‐mediated) and, unlike PACPX, had no effect on coronary perfusion pressure (A2‐mediated). Neither NPC 205 or PACPX had significant competitive inhibitory effects on rat heart phosphodiesterase III activity in vitro. Together, the results suggest that NPC 205 is a highly potent, selective, and competitive antagonist of adenosine A1 receptors and should be useful for examining the physiological significance of A1 receptors in vitro and in vivo.
Effect of repeated administration of clonidine on adrenergic, cholinergic (muscarinic), dopaminergic, and serotonergic receptors in brain regions of rats
Authors: Gulati Anil , Hussain Ghazala , Srimal Rikhab Chand 
Published: January 2005

AbstractClonidine (0.1 mg/kg) or its vehicle was administered orally to rats for 2 months. A significant decrease in mean blood pressure was observed in clonidine treated rats. Chronic administration of clonidine in rats produced alterations in central receptors. In hypothalamus and medulla, clonidine in treatment increased the Bmax value of 3H‐dihydroergocryptine binding to α‐adrenergic receptors. In cortex, clonidine treatment increased the Bmax value of 3H‐spiroperidol binding to dopaminergic receptors. Clonidine treatment produced a decrease in the Bmax value in cortex while in hypothalamus and medulla, an increase in the Bmax value of 3H‐quinuclydinyl benzylate (QNB) binding to muscarinic receptors was observed. In medulla, clonidine treatment increased the Bmax value of 3H‐5‐hydroxytryptamine (HT) binding to 5‐HT1 receptors. No change was observed in dissociation constant (Kd) values of any 3H‐ligand in any brain region. In vitro studies showed interaction of clonidine with 3H‐dihydroergocryptine and 3H‐QNB. It can be concluded from the present study that chronic administration of clonidine produces an up‐regulation of α‐adrenergic, cholinergic (muscarinic), and serotonergic (5‐HT1) receptors in brain regions mainly involved in cardiovascular regulation.
Hepatoprotective activity of picroliv, the active principle of Picrorhiza kurrooa, on rat hepatocytes against paracetamol toxicity
Authors: Visen P. K. S. , Shukla Binduja , Patnaik G. K. , Kaul Surabhi , Kapoor N. K. , Dhawan B. N. 
Published: January 2005

AbstractPicroliv, the active principle an iridoid glycoside mixture isolated from the plant Picrorhiza kurrooa, showed dose‐dependent (0.75–12 mg/kg × 7 days) protective activity on isolated hepatocytes (ex vivo) against paracetamol‐induced hepatic damage in rats. It increased the percent viability of the hepatocytes. Picroliv also restored the normal values of enzyme (glutamic oxaloacetic transaminase [GOT], glutamic‐pyruvic transaminase [GPT], and alkaline phosphatase) both in the isolated hepatocyte suspension as well as in the serum. Picroliv was found to be more potent than silymarin, a known hepatoprotective agent.
The effect of denbufylline (BRL 30892) on cortical pO2, pH, and microflow in a rat model of focal cerebral ischaemia
Authors: Angersbach Dieter 
Published: January 2005

AbstractThe effects of denbufylline (DBF), a novel xanthine derivate, have been investigated in a rat model of focal cerebral oligaemia. In this model a small (15–20 mm2) oligaemic area was produced by occlusion of pial arteries with a diameter of ca. 100 μm. The oligaemic area was characterized by a marked fall in cortical microflow, pO2, and pH, this being indicative of severe impairment of tissue nutrition leading to tissue acidosis. It is considered that the situation in this model may be analogous to that occurring in multi‐infarct dementia (MID) patients. DBF improved cerebral blood flow, enhanced cortical tissue oxygenation, and led to normalization of extracellular pH in the rat model of focal cerebral ischaemia. The results suggest that denbufylline ameliorates microcirculation and metabolism in brain areas affected by infarcts of small arteries.
CK‐2289 and milrinone in dogs with propranolol‐induced heart failure: Effect of ouabain
Authors: Greenberg Stanley S. , Touhey Beatrix , Hom Gary 
Published: January 2005

AbstractWe examined the interaction between ouabain and CK‐2289, a new bivalent inodilator, and compared their effect with that of milrinone on the hemodynamic and myocardial energetic parameters of anesthetized dogs with propranolol‐induced heart failure (PIHF). Mongrel dogs (13–19 kg) of either sex were anesthetized with pentobarbital sodium (35 mg/kg, i. v.) and instrumented for routine hemodynamic measurements using an open‐chest, artificially ventilated preparation. PIHF was produced by decreasing left ventricular (LV) dP/dTmax by 50% from control values with an initial infusion of 0.5 mg/kg of propranolol followed by continuous infusion of 0.02 to 0.08 mg/kg of propranolol to maintain PIHF. This was followed by infusion of saline (2 ml, i. v., n = 12/group) or ouabain (25 μg/kg, i. v., n = 12/group).Thirty min later saline and ouabain‐treated animals (4/group) were given 2 doses of saline (1 and 2 ml, i. v.), CK‐2289 (0.01 and 0.03 mg/kg, i. v.) or milrinone (0.03 and 0.1 mg/kg, i. v.) 30 min apart. Hemodynamic parameters were monitored continuously. Myocardial oxygen consumption (MVO2) was monitored 15 and 30 min after each dose of drug. CK‐2289 increased LV dP/dTmax and LV dP/dTmin by 60 and 120% and 42 and 43%, respectively. Mean arterial pressure decreased by 12% after the high dose of CK‐2289. CK‐2289 did not affect heart rate, while LV end diastolic pressure decreased by 5 mmHg. CK‐2289 increased LV work and did not affect or decrease LV contractile efficiency. Ouabain enhanced the myocardial energetic profile of CK‐2289 by allowing CK‐2289 to stimulate more work at a lower MVO2, thereby increasing myocardial efficiency. Milrinone had a profile similar to CK‐2289 but in ouabain‐pretreated animals with PIHF milrinone stimulated less work at the same MVO2, thus decreasing contractile efficiency. Thus, ouabain may enhance the myocardial energetic effects of CK‐2289.
Blood pressure effects of monoamine oxidase inhibitors in response to orally administered tyramine in the rat
Authors: Carroll Mary , Beek Otto 
Published: January 2005

AbstractThe reversible monoamine oxidase‐A inhibitors BW 1370U87, BW 616U76, brofaromine, and moclobemide, and the irreversible nonselective monoamine oxidase inhibitor phenelzine were compared for potentiation of the pressor response to oral tyramine. Conscious rats were pretreated with doses of the monoamine oxidase inhibitors sufficient to produce 80% inhibition of brain monoamine oxidase, and then were challenged with orally administered tyramine. Blood pressure was monitored prior to and after tyramine, and peak pressor responses were compared. At a dose of 15 mg/kg tyramine, the pressor response of BW 1370U87 was statistically similar to the vehicle control response. BW 616U76, brofaromine, and moclobemide elicited mild tyramine pressor effects, whereas phenelzine resulted in a marked elevation of blood pressure. Higher doses of tyramine elicited blood pressure elevations from all of the monoamine oxidase inhibitors.
Mitogen‐inducible prostaglandin G/H synthase: A new target for nonsteroidal antiinflammatory drugs
Authors: Xie Weilin , Robertson Donald L. , Simmons Daniel L. 
Published: January 2005

AbstractProstaglandins have been shown to be involved in many different biological processes, under both normal and pathological conditions. As the key enzyme in the production of prostaglandins and thromboxanes, prostaglandin GIH synthase (PGHS) has been well characterized, including extensive studies as a pharmacological target of the nonsteroidal antiinflammatory drugs (NSAIDs). The gene for this enzyme has been cloned, sequenced, and characterized from sheep, mouse, and human sources. Recently, a new form of this enzyme, a mitogen‐inducible PGHS (miPGHS), was identified. Comparisons between these two genes and their protein products have identified significant differences, including structural differences in the proteins and their mRNAs. The genes encoding these two isoenzymes are not coordinately regulated in cultured cells or in tissues. The discovery of this second form of PGHS may change our understanding of how NSAlDs exert their effects. miPGHS is believed to be a new, unique target of NSAIDs which could have a different sensitivity to many of these drugs, compared to the previously identified PGHS. © 1992 Wiley‐Liss, Inc.
A computerized system for measuring cell length of single isolated smooth muscle cells
Authors: Moummi Chafiq , Woodford Mark 
Published: January 2005

AbstractWe have developed a state‐of‐the‐art computerized system to measure the cell length (contraction/relaxation) of single isolated gastrointestinal smooth muscle cells in response to different drugs. The system is composed of a microscope to which a video camera is attached and a video monitor which is connected to the video camera output. The image on the TV screen is analyzed by a digital image processor. The data acquisition and initial analysis are done directly on a personal computer. The acquired data are sent immediately via a network to a database on a minicomputer. From this database, comprehensive data reports and graphs can be generated and hard copy obtained. The system was validated by testing the contractile activity of endothelin‐1 and the relaxant effect of isoproterenol on single smooth muscle cells isolated from the rat colon. This system offers a valuable pharmacological tool for drug screening to the pharmaceutical industry. © 1992 Wiley‐Liss, Inc.
Long‐term use of appetite suppressant medication: Rationale and recommendations
Authors: Stallone Daryth D. , Stunkard Albert J. 
Published: January 2005

AbstractWe propose a change in the use of “appetite suppressant” medication in the treatment of obesity: use it on a long‐term basis or not at all. This proposal is based on the theory that “appetite suppressant” medication acts primarily by lowering the regulated level of body weight. We review the concept of the regulation of body weight and present evidence that body weight is regulated in animals of normal weight and in some obese animals. We show that the concept of the regulation of body weight also applies to variations of body weight produced by endogenous factors, such as those related to hibernation, as well as by experimental interventions, such as brain lesions and “appetite suppressant” medication. Evidence of body weight regulation in normal weight and obese humans is presented and clinical significance discussed. We conclude with a discussion of a new role for “appetite suppressant” medication in the treatment of obesity. © 1992 Wiley‐Liss, Inc.
SCH 39166, a novel dopamine D1 receptor antagonist: In vitro investigation of its glucuronidation and potential species differences
Authors: Tedford Clark E. , Ruperto Vilma B. , Coffin Vicki L. , Cohen Mary , Libonati Michele , Barnett Allen 
Published: January 2005

AbstractSCH 39166 is a novel benzonaphthazepine that is a selective dopamine D1 receptor antagonist. It is currently undergoing clinical trials in humans for possible use as an antipsychotic medication. To date, no studies have been presented describing the metabolism of SCH 39166. Therefore, the present studies investigated the possible in vitro glucuronidation of SCH 39166 from both rodent and squirrel monkey liver microsomes. Comparisons were made with the classic D1 antagonist, SCH 23390, a benzazepine which undergoes extensive glucuron dation in the rat. Additionally, dose response and duration of action of SCH 39166 on the conditioned avoidance paradigm (CAR) in both rats and squirrel monkeys were compared to the dose response and duration of action of SCH 23390 in these species. Results demonstrated that 3H‐SCH 39166 was glucuronidated by both rat and monkey liver microsomes. In studies with rat liver microsomes, the rate of glucuronidation of SCH 39166 and the affinity for the glucuronosyltransferase enzyme were equivalent to those of SCH 23390. In vivo behavioral studies also indicated no differences in either the dose‐response curves or the time course of behavioral effects for either D1 antagonist after oral administration in the rat. In contrast, the rate of glucuronidation in squirrel monkey liver microsomes of SCH 23390 was 3–4 times faster than that of SCH 39166. Moreover, these findings consistent with in vivo behavioral studies in squirrel monkeys, in which the duration of action of SCH 23390 was much shorter than SCH 39166. © 1992 wiley‐Liss, Inc.
Comparative pharmacology of dothiepin, its metabolites, and other antidepressant drugs
Authors: Heal David , Cheetham Sharon , Martin Keith , Browning John , Luscombe Graham , Buckett Roger 
Published: January 2005

AbstractThe pharmacology of dothiepin and its human metabolites, northiaden, dothiepin sulfoxide, and northiaden sulfoxide, has been studied to determine whether the latter contribute to the therapeutic or side effects profile of the parent tricyclic antidepressant. In vitro, dothiepin was a potent noradrenaline and 5‐hydroxytryptamine (5‐HT) uptake inhibitor, while its secondary amine metabolite, northiaden, was selective for noradrenaline. However, the sulfoxide metabolites were almost inactive as uptake inhibitors. Dothiepin and northiaden prevented the ptosis produced by tetrabenazine in mice and reserpine in rats and increased the mobility of mice in the Porsolt test. After repeated administration, both drugs decreased β‐adrenoceptor number and stimulation of the receptor‐linked adenylate cyclase by noradrenaline. Dothiepin had a higher affinity than northiaden for histamine H1, muscarinic and various adrenergic and 5‐HT receptors in vitro, whereas the sulfoxide metabolites were inactive. Overall, the data indicate northiaden almost certainly contributes to the therapeutic actions of dothiepin, but the sulfoxide metabolites do not. However, the latter are also unlikely to produce any side effects. A comparison of dothiepin with other tricyclics revealed important divergences in the profiles of uptake inhibition and receptor affinity. Thus, dothiepin is generally similar to imipramine in its pharmacology, but it differs considerably from amitriptyline and doxepin. © 1992 Wiley‐Liss, Inc.
Microgram doses of chlordiazepoxide and diazepam do not increase punished responding in the rat
Authors: Pollard Gerald T. , Howard James L. 
Published: January 2005

AbstractMicrogram doses of chlordiazepoxide and diazepam injected intraperitoneally (i.p.) have been reported to change rodent behavior, notably in two observational procedures that predict anxiolysis. We tested half‐log doses from 0.03 to 10 mg/kg in the Geller‐Seifter conflict preparation in the rat. Only doses in the milligram range showed any tendency to increase punished responding. The results do not support the hypothesis that microgram doses might be anxiolytic. © 1992 Wiley‐Liss, Inc.
Purinoceptor nomenclature: A status report
Authors: Abbracchio Maria P. , Cattabeni Flaminio , Fredholm Bertil B. , Williams Michael 
Published: January 2005

AbstractIn the field of purinoceptors, the P1‐adenosine and P2‐ATP system proposed by Burnstock some 15 years ago has provided a cornerstone for receptor nomenclature [Burnstock and Kennedy, 1985: Gen Pharmacol 16:433–440.] For the adenosine/P1 receptor class, the generally accepted nomenclature has been that of A1 and A2, while P2 receptor have been defined as P2x, P2y, and so on. The incorporation of newer receptors, characterised either by the actions of available compounds on defined tissues systems or by the cloning and expression of purinoceptors, into this framework provides the challenge of melding the “old” with the “new”. An open meeting of the IUPHAR Purine Receptor Nomenclature Subcommittee held at the Purine Club's “Purine '92” in Milan in June of 1992 focused on this issue with input from world leaders in the area of purine research. It was recommended from this meeting that adenosine receptors, in addition to the classical A1, A2a, and A2b receptors, be further described by numerical subscript, i.e., A3, A4, until such time as pharmacological and molecular biological data provided evidence for their relationship, if any, to the A1/A2, classes. For ATP and other purine nucleotide receptors, subtypes of which were designated by letters rather than numbers, the P2X and P2Y, receptors proposed by Burnstock major families of P2 receptors utilizing ligand‐gated cation channels and G‐proteins, respectively. Some concerns were expressed in regard to the apparent random walk through the alphabet in of the IUPHAR nomenclature initiative. © 1993 Wiley‐Liss, Inc.
Neuromodulatory roles of purines
Authors: Fredholm Bertil B. , Johansson Björn , van der Ploeg Ingeborg , Hu Ping Sheng , Jin Shaoyu 
Published: January 2005

AbstractIn the present overview we focus on two aspects: (a) the role of adenosine as an endogenous cerebroprotective agent and (b) the possible significance of adenosine‐dopamine interactions. Adenosine is a normal constituent of the brain extracellular environment. Its levels greatly increase upon neuronal excitation or as a consequence of decreased supply of metabolic substrates. Via its receptors it tends to limit its own formation in several ways. By increasing blood flow and glucose uptake it increases substrate supply. By decreasing the release of excitatory neurotransmitters and by causing hyperpolarization it decreases energy demand. This suggests a role as an endogenous cerebroprotective agent, something which is supported by several lines of pharmacological evidence.The adenosine A2a receptor is enriched in dopamine rich‐areas of the brain and it has been found to be colocalized with dopamine D2 receptors on medium‐sized spiny neurons in the striatum. Recent evidence shows that A2 agonists decrease agonist binding to dopamine D2 receptors. Furthermore, adenosine receptor antagonists have been shown to produce behavioural effects that are due to enhanced dopaminergic neurotransmission. It is suggested that the A2‐ D2‐receptor interactions may explain some of the stimulatory effects of low doses of caffeine. © 1993 Wiley‐Liss, Inc.
Differential effects of early chronic lead exposure on postnatal rat brain NMDA, PCP, and adenosine A1 receptors: An autoradiographic study
Authors: Brooks William J. , Petit Ted L. , Leboutillier Janelle C. , Nobrega Jose N. , Jarvis Michael F. 
Published: January 2005

AbstractThe deleterious effects of postnatal lead (Pb) exposure on neural development, synaptic plasticity, and cognitive function have been well documented in laboratory animals. While the exact mechanisms by which Pb produces long‐lasting neurotoxicity remain unknown, recent evidence suggests that Pb may interact with and/or disrupt the N‐methyl‐D‐aspartate/phencyclidine receptor complex and the associated ion channel. In addition to perturbations of excitatory amino acid neurotransmission, chronic Pb exposure may also have deleterious effects on inhibitory mechanisms such as that provided by purinergic neuromodulation. In order to further examine the possibility that alterations of both excitatory and inhibitory neurotransmission may contribute to the neurotoxic actions of Pb, the effects of early Pb exposure on ligand binding to postnatal rat brain N‐methyl‐D‐aspartate (NMDA), phencyclidine (PCP), and adenosine A1 receptors were examined using quantitative autoradiography techniques. Rat pups nursed mothers exposed to 4% PbCO3 in their diet or a Na2CO3 control diet from postnatal day 1 (P1) to P25. At P25, rats were sacrificed and the regional distributions of brain NMDA, PCP, and adenosine A1 receptors were examined. Chronic lead exposure was found to produce a specific increase in [3H]CGP 39653 binding to NMDA receptors in the hippocampus. [3H]1‐(1‐[2‐thienyl)cyclohexyl]‐piperdine ([3H]TCP) binding to PCP receptors was largely unaffected by the chronic Pb treatment. In contrast, [3H]cyclohexyladenosine ([3H]CHA) binding to adenosine A1 receptors was markedly reduced in many brain regions with the largest decreases observed in the cerebellum. These results indicate that neonatal Pb exposure produces a specific alteration of both excitatory and inhibitory neuromodulatory mechanisms in the postnatal rat forebrain that may underlie the behavioral hyperactivity and increased seizure sensitivity associated with Pb neurotoxicity. © 1993 Wiley‐Liss, Inc.
Role of serotonin in ethanol abuse
Authors: Wallis Cleatus J. , Rezazadeh S. Mehdi , Lal Harbans 
Published: January 2005

AbstractSeveral subclasses of serotonin receptors (5‐HT1a, 5‐HT1b, 5‐HT1c, 5‐HT2, and 5‐HT3) have been implicated in the control of ethanol (EtOH) related behaviors, such as: (1) voluntary EtOH consumption, (2) anxiety occurring during EtOH withdrawal (EW), (3) interoceptive stimuli produced by EtOH, and (4) modulation of EtOH intoxication. Serotonin modulation of neuronal excitability and modulation of hormone release may be important mechanisms contributing to the development and/or maintenance of ethanol tolerance/dependence by modulating emotional behavior (anxiety), homeostasis, and adaptive processes. This review examines our current understanding of serotonin's contribution to ethanol abuse. © 1993 wiley‐Liss, Inc.
Interaction of berbamine and chloroquine or artemisinin against chloroquine‐sensitive and ‐resistant plasmodium falciparum in vitro
Authors: Ye Zuguang , Van Dyke Knox , Yang Baizhen 
Published: January 2005

AbstractAntimalarial activity of berbamine (BB), alone or in combination with chloroquine (CQ) or artemisinin (qinghaosu, QHS), was studied using CQ‐sensitive and ‐resistant strains of Plasmodium falciparum in vitro. BB was found to have antimalarial effects with IC50 values of 603 and 359 nM, respectively, for the drug‐sensitive and ‐resistant strains of P. falciparum, indicating that BB exhibited some selective antimalarial activity against the drug‐resistant parasite. Its antimalarial efficacy and selectivity appeared to be less than that of tetrandrine (TT), however, when BB was combined with CQ, an antagonistic interaction was found against the CQ‐sensitive parasite, while a potentiating antimalarial action was observed with the CQ‐resistant parasite. When BB was tested in combination with QHS, a complex interaction was found—one was additive for the CQ‐sensitive parasite and the other was potentiating for the CQ‐resistant parasite. The above data suggested that the BB combination with either CQ or QHS is a promising candidate for an antimalarial remedy to treat at least CQ‐resistant falciparum parasites which cause malaria. © 1993 wiley‐Liss, Inc.