The Open Pharmacology Journal最新文献

{"title":"Elucidating GABAA and GABAB Receptor Functions in Anxiety Using theStress-Induced Hyperthermia Paradigm: A Review","authors":"C. Vinkers, J. Cryan, B. Olivier, L. Groenink","doi":"10.2174/1874143601004010001","DOIUrl":"https://doi.org/10.2174/1874143601004010001","url":null,"abstract":"Exposure to acute psychological or physical stress increases core body temperature (stress-induced hyperthermia, SIH) which is part of the autonomic stress response. SIH is used as a putative rodent anxiety paradigm in which anxiolytic drugs reduce the SIH response. The predictive validity of the SIH paradigm has proven to be good, making it suitable to detect the putative anxiolytic properties of drugs. So far, GABAA receptor agonists including benzodiazepines and hypnotics have proven to attenuate the SIH response. The GABAA receptor has been known to be closely involved in the acute stress response. Also, the recent development of compounds with selective efficacy for differentsubunits at the benzodiazepine site of the GABAA receptor has renewed interest for the therapeutic potential of GABAergic drugs. Moreover, metabotropic (GABAB) receptor agonists reduce the SIH response. GABAB receptors are ubiquitously expressed in the central nervous system, and there is evidence for a role of the GABAB receptor in anxiety. Thus, both drugs acting on the GABAA and the GABAB receptor are generally able to attenuate the SIH response, and this review presents a detailed overview of the effects of both drug classes on the SIH response. As the GABA receptor family is diverse and complex, this paradigm may contribute to the elucidation of the putative effects of GABAergic drugs in emotional disorders such as anxiety and depression","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"71 2 1","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2010-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89161379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QT Interval Prolongation and Atypical Proarrhythmia: Monomorphic Ventricular Tachycardia with Trimebutine","authors":"M. Schiariti, A. Saladini, A. Placanica, Marta Saolini, P. Puddu","doi":"10.2174/1874143600903010032","DOIUrl":"https://doi.org/10.2174/1874143600903010032","url":null,"abstract":"A 59-year old woman was admitted at emergency for palpitation and dizziness. Medication history showed trimebutine 450 mg daily, because of meteorism, increased to 450 mg TID a week earlier. At admittance, sustained monomorphic ventricular tachycardia was interrupted by 100 mg intravenous lidocaine and a largely prolonged QTc (523 ± 12 ms) was seen. Discontinuation of trimebutine achieved normalisation of QTc (420 ± 10 ms, p<0.001). This is the first report in man to illustrate a probable proarrhythmic action of trimebutine. A weak inhibitory effect on both rapid and slow components of the delayed rectifier in guinea-pig ventricular myocytes calls for further investigations in human myocardial tissues. Trimebutine inhibition of Na + and Ca ++ channels in cardiac tissues of rabbits and guinea-pigs also call for further studies in human myocardial tissues.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"2007 1","pages":"32-36"},"PeriodicalIF":0.0,"publicationDate":"2009-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82493460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Perspectives of Angiotensin-(1-7) in the Treatment of Cardiovascular Disease","authors":"C. Höcht, M. Mayer, C. Taira","doi":"10.2174/1874143600903010021","DOIUrl":"https://doi.org/10.2174/1874143600903010021","url":null,"abstract":"In the last decade, new biologically active components of the renin-angiotensin system were found. Angiotensin-(1-7) (Ang-(1-7)), a metabolite of angiotensin I and angiotensin II (Ang II), is considered the most pleiotropic component of the renin-angiotensin system, acting as a counterregulatory mediator of Ang II. Ang-(1-7) exerts beneficial effects on the cardiovascular system, including reduction of blood pressure, myocardial antihypertrofic and antifibrotic actions, and reversal of renal dysfunction, among others. Recent discovery of enzymatic pathways involved in Ang-(1-7) synthesis, such as the angiotensin-converting enzyme-2 (ACE2) and the existence of a specific receptor to this heptapeptide, the Mas receptor, have increased interest in the design of therapeutic strategies aimed at increasing the biological actions of Ang-(1-7). ACE inhibitors, AT1 receptor blockers and aldosterone antagonists enhance Ang-(1-7) levels by different mechanisms. Actually, non-peptidic Ang-(1-7) agonists and ACE2 activators are under development and could have a role in the treatment of cardiovascular diseases. The aim of the present review is to describe the biochemical and physiological actions of Ang-(1-7), the therapeutic strategies designed to enhance Ang-(1-7) activity foccusing in their possible role and limitations in the treatment of cardiovascular disease.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"5 1","pages":"21-31"},"PeriodicalIF":0.0,"publicationDate":"2009-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90337671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of LY379268, A Selective Agonist of mGLu2/3 Receptors, on Isolation-Induced Aggression in Male Mice","authors":"J. Navarro, M. J. Luque, M. Martín-López","doi":"10.2174/1874143600903010017","DOIUrl":"https://doi.org/10.2174/1874143600903010017","url":null,"abstract":"Recent studies indicate that glutamate metabotropic receptors (mGlu) 1 and 5 are involved in the regulation of aggressive behaviour. Brain distribution of mGlu2/3 receptors suggests that they may also play important roles in emotional responses, including aggression. This study examines the effects of LY379268 (0.254 mg/kg, ip), a selective agonist of the mGlu2/3 receptors, on agonistic interactions between male mice using an animal model of isolation-induced aggression. Individually housed mice were exposed to anosmic “standard opponents” 30 min after drug administration. Ten min of diadic interactions were staged between a singly housed and an anosmic mouse in a neutral area. The encounters were videotaped and the accumulated time allocated by subjects to ten broad behavioural categories was estimated using an ethologically based analysis. LY379268 (2 mg/kg) significantly reduced attack behaviour, as compared with the control group, without affecting immobility, whereas the highest dose of the drug (4 mg/kg) also decreased offensive behaviours (threat and attack), but with a marked increase of immobility (non-selective effect). These results indicate that mGlu2/3 receptors might be implicated in the modulation of aggression.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"14 1","pages":"17-20"},"PeriodicalIF":0.0,"publicationDate":"2009-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84273089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence for Excitatory and Inhibitory Amino Acids Participation in theNeuropharmacological Activity of Alpha- and Beta-Amyrin Acetate","authors":"G. Aragão, L. M. Carneiro, Antônio P.F. Juniora, P. Bandeira, T. L. Lemos, G. Viana","doi":"10.2174/1874143600903010009","DOIUrl":"https://doi.org/10.2174/1874143600903010009","url":null,"abstract":"We evaluated the neuropharmacological profile of acetylated alpha- and beta-amyrin (AcAMY) obtained by the acetylation of the isomeric mixture of alpha- and beta-amyrin isolated from Protium heptaphyllum. Male Swiss mice were administered with AcAMY (2.5, 5, 10 and 25 mg/kg, i.p.), and anticonvulsant (pentylenetrazole- and pilocarpine-induced convulsions), sedative (barbiturate-induced sleep and open field tests) and anxiolytic (elevated plus maze test) activities were studied. Results showed that AcAMY administered intraperitoneally or orally, protected the animals against penty- lenetetrazole- but not against pilocarpine-induced convulsions. The drug increased both the latency to the 1 st convulsion and the latency to death. The barbiturate-induced sleeping time was also increased, as well as the ethyl ether-induced sleeping time, confirming the sedative nature of AcAMY. The acute administration of AcAMY also produced an anx- iolytic effect. After the sub-chronic administration, both sedative and anxiolytic effects were manifested, at the two higher doses. Amino acids measurements in brain areas of mice treated with AcAMY (25 mg/kg, i.p., for 7 days) showed an 89% increase in tyrosine levels, in the hippocampus. In the striatum, tyrosine and taurine were increased by 97 and 79%, re- spectively, while decreases in the levels of aspartate, GABA and glutamate of 72, 55 and 60%, respectively were ob- served. In conclusion, our results showed that AcAMY presents sedative, anxiolytic and anticonvulsant properties. Al- though the drug mechanism of action is not completely clarified, it seems to involve a decrease in excitatory amino acids and an increase of inhibitory amino acids. Furthermore, the GABAergic system may also play a role.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"25 12","pages":"9-16"},"PeriodicalIF":0.0,"publicationDate":"2009-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91491676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time of Day and Length of Antidepressant Drug Administration Influence Brain-Derived Neurotrophic Factor and TrkB Levels in Rat Brain","authors":"Megan E. Kozisek, N. Qutna, D. Bylund","doi":"10.2174/1874143600903010001","DOIUrl":"https://doi.org/10.2174/1874143600903010001","url":null,"abstract":"The expression of brain-derived neurotrophic factor (BDNF) mRNA and protein and its primary receptor, TrkB mRNA shows circadian oscillations in adult rats; however it has been unclear if juvenile rats also display a similar pattern in circadian oscillations. We determined the levels of BDNF and TrkB mRNA and of BDNF protein at four separate time points during a 24 hperiod in the hippocampus and frontal cortex. The expression of BDNF and TrkB undergoes diurnal oscillation in adult and postnatal day 21 rats, but no significant variation is present in postnatal day 13 rats. Antidepressant drug treatment also is known to influence BDNF and TrkB levels. However, the reported effects of antidepressant drug treatment on BDNF and TrkB are highly variable and may be influenced by multiple factors, including detection method, class of antidepressant drug, and length of administration. BDNF mRNA levels were decreased significantly in the hippo- campus after acute desipramine (a tricyclic antidepressant) treatment compared to control. BDNF mRNA and protein lev- els, as well as TrkB mRNA levels, were unchanged in adult rats after subchronic and chronic treatment with either de- sipramine or escitalopram (a selective serotonin reuptake inhibitor) and treatment consistent with several reports in the lit- erature. This study defines several important factors that must be taken into account when comparing BDNF and TrkB levels both within and among studies.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"3 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2009-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89006517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping Biopharmaceutical Innovation and Diffusion: How the Second Translational Block (T2) Shapes Drug Diffusion","authors":"Joshua P Cohen, Laura B Faden, K. Getz","doi":"10.2174/1874143600802010089","DOIUrl":"https://doi.org/10.2174/1874143600802010089","url":null,"abstract":"In the US, there is a vigorous public debate on the merits of biopharmaceutical innovations and their diffusion. There is virtual unanimity about the importance of maintaining a steady stream of biopharmaceutical innovations, to which patients should have timely access. However, the debate's participants are cognizant that the effects of innovation and diffusion on health outcomes, health care spending, and incentives for future innovation, must be weighed against one another. First, we performed a Medline literature review to map the innovation diffusion process, combining the search terms \"in- novation,\" \"diffusion,\" and \"pharmaceutical.\" Second, we conducted a survey of 190 physicians to examine their valua- tion of the innovativeness and rate of diffusion of 20 new molecular entities (NMEs). Third, we collected data from the Centers for Medicare and Medicaid Services (CMS) Formulary Finder to assess payers' valuation of the innovativeness of the 20 NMEs in question. Based on our literature review, we identified the key stakeholders involved in the innovation diffusion process. Further- more, we highlighted the changing landscape of translational movers and shakers, tracing the emergence of T2 barriers, emanating largely from third party payer formulary management. Our empirical analysis suggests payers are exerting influence on physicians' prescribing decisions, while the role of pa- tients and pharmaceutical firms has diminished somewhat. Payers directly affect prescribing decisions through the use of formularies, and indirectly by funding evidence-based continuing medical education.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"6 1","pages":"89-106"},"PeriodicalIF":0.0,"publicationDate":"2008-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79084791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Foundation of Toxicology’s Dose x Time = Constant Paradigm in Physics","authors":"K. Rozman","doi":"10.2174/1874143600802010087","DOIUrl":"https://doi.org/10.2174/1874143600802010087","url":null,"abstract":"The relationship dose x time = constant (mg · hr) has been reported in many toxicological experiments during the past 100 years. It was handled as a curiosity until Rozman and Doull pointed out that it can be found in every experi- ment that is conducted under equilibrium conditions which is called steady state in pharmacology and toxicology. This manuscript suggests that this relationship is consistent with the most basic laws of physics.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"19 1","pages":"87-88"},"PeriodicalIF":0.0,"publicationDate":"2008-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83418698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nε-(Carboxymethyl)Lysine-Induced Choroidal Angiogenic Potential Facilitates Retinal Neovascularization in Advanced-Diabetic Rat In Vitro","authors":"Shinjiro Kobayashi, M. Nomura, Tatsuo Takahashi, Miho Suzuki, R. Nagai, N. Hagino","doi":"10.2174/1874143600802010079","DOIUrl":"https://doi.org/10.2174/1874143600802010079","url":null,"abstract":"N  -(Carboxymethyl)lysine (CML) over-stimulates choroidal neovascularization in vitro in streptozotocin (STZ)-diabetic rat. In this study, we investigated the effects of CML-induced choroidal angiogenic potential on retinal neovascularization during the course of STZ-induced diabetes in rats. Retinal and choroidal explants were isolated from the same eyeball of early-diabetic, advanced-diabetic and age-matched normal rats. When retinal explant was co-cultured with early-diabetic choroidal explant, the number of retinal microvessels was significantly decreased. When retinal ex- plant was co-cultured with advanced-diabetic choroidal explant, the number of retinal microvessels was significantly in- creased. Anti-CML antibody blocked the retinal changes caused by co-culture with both early-diabetic and advanced- diabetic choroidal explant. Antibodies against TNF  and VEGF reduced the number of retinal microvessels in the co- culture with advanced-diabetic choroidal explant. These results indicate that the CML-induced choroidal activity is asso- ciated with the angiogenic actions of TNF  and VEGF on retinal capillaries in advanced diabetes. During the course of diabetic retinopathy, different actions on retinal neovascularization may operate.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"93 1","pages":"79-86"},"PeriodicalIF":0.0,"publicationDate":"2008-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79436939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidant Activity of a Cissus verticillata Fraction and Tyramine, its Bioactive Constituent, on Alloxan-Induced Diabetic Rats","authors":"C. S. Lino, T. Sales, F. Alexandre, J. M. Ferreira, D. F. Sousa, P. B. Gomes, Jeferson Falcão DO Amaral, F. D. Maia, E. Silveira, M. Queiroz, F. Sousa, G. Viana","doi":"10.2174/1874143600802010063","DOIUrl":"https://doi.org/10.2174/1874143600802010063","url":null,"abstract":"In the present study, the antioxidant activity of a methanol soluble fraction (MSF) from Cissus verticillata, used in Brazil and elsewhere as a hypoglycemic and antidiabetic medicinal plant, and tyramine (TYR), one of its main bioac- tive constituents, was assessed. For this, male Wistar rats were submitted to alloxan injection (40 mg/kg, i.v.) in order to induce a diabetic state and, 48 h later, glycemia was determined. Animals were distributed into groups: normal controls (NC); diabetic controls (DC); DC plus MSF; and DC plus TYR. Another group was treated with glibenclamide (GLI), used as a positive control. After 5-day treatments, animals were sacrificed for liver dissection, and determination of anti- oxidant markers such as thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), catalase and nitrite concentrations. The antioxidant effect was also evaluated on the pentobarbital-induced sleeping time, before and after CCl4 treatment. Under our experimental conditions, diabetic rats did not present any alteration in liver lipid peroxidation, before (DC) or after treatments with the MSF; TYR or GLI, as compared to normal controls (NC). Levels of GSH were significantly increased in 79% in DC, as related to NC, and the effects were partially reversed in diabetic rats, after MSF treatments at the higher dose. However, while similar effects were observed after TYR and GLI, both drugs brought val- ues of GSH to normality. The DC group had increased liver catalase activity, as compared to NC, and these effects were partially reversed by MSF and almost completely by TYR and GLI. Significant increases were also detected in nitrite concentrations in livers of DC, as an index of free radical formation, and a large reduction was observed after MSF, TYR and GLI treatments of diabetic rats, as compared to NC. MSF and TYR also prevented prolongation of the pentobarbital- induced sleeping time by CCl4, suggesting hepatoprotective and anti-oxidative effects. In conclusion, we showed that the antioxidant activity probably plays an important role in the antidiabetic effect of C. verticillata, and TYR is at least in part responsible for this property.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"9 1","pages":"63-69"},"PeriodicalIF":0.0,"publicationDate":"2008-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84740150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}