bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trialkylglycines: A New Family of Compounds with in Vivo Neuroprotective Activity
Authors: Sánchez‐Pérez Ana M. , Montoliu Carmina , Felipo Vicente 
Published: August 2010

ABSTRACTGlutamate neurotoxicity is involved in the pathogenesis of neurodegenerative disorders such as Huntington's, Parkinson's and Alzheimer's diseases. It plays also a major role in the neuronal damage that occurs in brain ischemia and head trauma. Finding molecules that prevent or reverse glutamate neurotoxicity (excitotoxicity) is, therefore, of great interest. Strategies aimed at this end include the screening of libraries of compounds synthesized by combinatorial chemistry to find molecules that prevent neuronal death in vitro and in vivo. A library of trialkylglycines was screened to assess whether they prevent glutamate‐induced neuronal death in primary cultures of cerebellar neurons. Two types of trialkylglycines have been found that significantly reduce the incidence of glutamate‐induced neuronal death. The first type includes two compounds (referred to as 6–1–2 and 6–1–10) that efficiently prevent glutamate or NMDA‐induced neuronal death. They also prevent excitotoxicity in vivo as assessed by using two animal models of excitotoxicity: acute intoxication with ammonia and a model of cerebral ischemia in rats. Trialkylglycines 6–1–2 and 6–1–10 prevent ammonia‐induced (NMDA receptor‐mediated) death of mice and neuronal degeneration in the model of cerebral ischemia. The trialkylglycines of the second type act as open channel blockers of the NMDA receptor. The first group of trialkylglycines does not block NMDA receptor channels and does not affect the gluta‐mate‐nitric oxide‐cGMP pathway. Their molecular target has not yet been identified.These two types of trialkylglycines (especially those that do not affect NMDA receptor function) might represent effective drugs for the treatment of neurodegeneration. They are likely to be well tolerated and have fewer side effects than NMDA receptor antagonists.
Neuropharmacological Profile of an Atypical Antipsychotic, NRA0562
Authors: Hirota Shiho , Kawashima Naoya , Chaki Shigeyuki , Okuyama Shigeru 
Published: August 2010

ABSTRACTSchizophrenia is a serious and disabling psychiatric disorder affecting approximately 1% of the world's population. Anew generation of atypical antipsychotics has been introduced over the past decade. These atypical antipsychotics have comparable or greater efficacy than traditional antipsychotics in the treatment of the psychotic symptoms of schizophrenia and a much improved neurologic side effect profile. This paper reviews the pharmacological efficacy and safety of a potential atypical antipsychotic, NRA0562.NRA0562 has a high affinity for dopamine D1, D2L, D4.2, 5‐HT2Areceptors as well as α1‐adrenoceptors, and has a moderate affinity for H1receptors. NRA0562 strongly binds to 5‐HT2Areceptors and α1‐adrenoceptors in the frontal cortex, its binding to striatal D2receptors is weaker, similar to that of clozapine.NRA562 displayed potent antipsychotic activities in animal models of schizophrenia, such as methamphetamine (MAP)‐induced hyperactivity, apomorphine‐induced disruption of pre‐pulse inhibition and conditioned avoidance test. NRA0562 is more potent in reversing the inhibitory effects of MAP at A10 than at A9 dopamine neurons. It increased Fos‐like immunoreactivity in the nucleus accumbens more effectively than in the dorsolateral striatum, indicating that NRA0562 has the profile of an atypical antipsychotic.In vivoassays for extrapyramidal side effect liability showed that NRA0562 has a low rate of neurological side effects. Thus, NRA0562 may have unique antipsychotic activity with a lower propensity for extrapyramidal side effects.
The Selective Norepinephrine Reuptake Inhibitor Antidepressant Reboxetine: Pharmacological and Clinical Profile
Authors: Hajós Mihály , Fleishaker Joseph C. , Filipiak‐Reisner Jacqueline K. , Brown Mark T. , Wong Erik H. F. 
Published: August 2010

ABSTRACTReboxetine is the first commercially available norepinephrine reuptake inhibitor developed specifically as a first line therapy for major depressive disorder.In vitroandin vivopharmacological studies indicated that reboxetine methanesulphonate has high affinity and selectivity for the human norepinephrine transporter over the serotonin and dopamine transporters. Pharmacological specificity is further demonstrated by the absence of affinity for 45 transmitter receptors and CNS targets.Pharmacokinetic studies demonstrated that reboxetine is suitable for twice daily administration (8–10 mg/day) and that it exhibits minimal drug‐drug interactions. The starting dose of reboxetine should be reduced in the elderly, in patients with renal or hepatic impairment, or in patients receiving potent CYP3A inhibitors. A total of 20 phase II/III clinical studies comprising placebo‐controlled, active comparator‐controlled and open‐label uncontrolled studies in both short‐term and long‐term treatment of major depression have been conducted. In the treatment of major depression, reboxetine was superior to placebo in 5 of 12 short‐ or long‐term placebo‐controlled studies and was comparable in efficacy to active comparators in 3 out of 3 active‐controlled studies. Unlike conventional tricyclic antidepressants (TCAs), reboxetine had only minimal sedative and cardiovascular liabilities, probably due to increased pharmacological specificity of reboxetine as compared with TCAs. Unlike serotonin reuptake inhibitors, this selective and specific norepinephrine reuptake inhibitor demonstrated a distinct side‐effect profile with diminishing sexual dysfunction and GI side effects. The availability of this agent has afforded patients suffering from major depressive disorder a new class of agents to combat the debilitating consequence of this psychiatric disease. The demonstrated pharmacological specificity of this compound has provided the psychopharmacology community with a tool to elucidate the role of norepinephrine in brain functions. Testing this agent in different animal models has enabled the exploration of the role of modulation of norepinephrine tone in the therapy of CNS disorders beyond depression.
Role of Hyperforin in the Pharmacological Activities of St. John's Wort
Authors: Zanoli Paola 
Published: August 2010

ABSTRACTThe phloroglucinol derivative hyperforin has been recently shown to be a major antidepressant component in the extract ofHypericum perforatum.Experimental studies clearly demonstrated its activity in different behavioral models of depression. Moreover clinical studies linked the therapeutic efficacy ofHypericumextracts to their hyperforin content, in a dose‐dependent manner.The molecular mechanism of action of hyperforin is still under investigation. Hyperforin has been shown to inhibit, like conventional antidepressants, the neuronal uptake of serotonin, norepinephrine and dopamine. However, hyperforin inhibits also the uptake of γ‐aminobutyric acid (GABA) and L‐glutamate. The uptake inhibition by hyperforin does not involve specific binding sites at the transporter molecules; its mechanism of action seems to be related to sodium conductive pathways, leading to an elevation in intracellular Na+concentration. Other additional mechanisms of action of hyperforin, involving ionic conductances as well synaptosomal and vesicular function, have been suggested. In addition to its antidepressant activity, hyperforin has many other pharmacological effectsin vivo(anxiolytic‐like, cognition‐enhancing effects) andin vitro(antioxidant, anticyclooxygenase‐1, and anticarcinogenic effects). These effects could be of clinical importance. On the other hand, the role of hyperforin in the pharmacological interactions occurring duringHypericumextract therapy must be fully investigated. Hyperforin seems to be responsible for the induction of liver cytochrome oxidase enzymes and intestinal P‐glycoprotein.Several pharmacokinetic studies performed in rats and humans demonstrated oral bioavailability of hyperforin fromHypericumextract. Only recently a new chromatographic method for detection of hyperforin in the brain tissue has been developed and validated. Taking into account the chemical instability of hyperforin, current efforts are directed to the synthesis of new neuroactive derivatives.
Dihydrexidine — The First Full Dopamine D1Receptor Agonist
Authors: Salmi Peter , Isacson Ruben , Kull Björn 
Published: August 2010

ABSTRACTThe functional role of dopamine D1receptors is still controversial. One reason for this controversy is that for a long time the only available agonists for in vivo characterization of dopamine D1receptors were benzazepines. Among them was the prototype dopamine D1receptor partial agonist, SKF 38393. The lack of a selective and fully efficacious dopamine D1receptor agonist hampered basic research on dopamine D1receptors and left the potential clinical utility of dopamine D1receptor agonists elusive. The research situation improved when the first potent full dopamine D1receptor agonist dihydrexidine, a phenanthridine, was introduced in the late 1980s. In contrast to SKF 38393, dihydrexidine was shown to stimulate cyclic AMP synthesis just as well or better than dopamine, and potently displaced [3H]SCH 23390 from rat and monkey striatal membranes. Also, dihydrexidine was the first dopamine D1receptor agonist that had potent antiparkinsonian activity in a primate model of Parkinson's disease. This finding suggested clinical utility for dopamine D1receptor agonists in Parkinson's disease and that this utility might be critically dependent on the intrinsic efficacy of the drug. Clinical utility for dopamine D1receptor agonists in other central nervous disorders might also be dependent on the intrinsic efficacy of the drug. However, even though studies with dihydrexidine as a pharmacological tool have pointed to the clinical use for dopamine D1receptor agonists, dihydrexidine's unfavorable pharmacokinetic profile and various adverse effects are likely to restrict or even preclude its use in humans. This review article provides an updated overview of the pharmacology of dihydrexidine and discusses possible clinical utility of dopamine D1receptor agonists in various central nervous system disorders.
Therapeutic Potential of Wogonin: A Naturally Occurring Flavonoid
Authors: Tai Man Chun , Tsang Shui Ying , Chang Lawrence Y. F. , Xue Hong 
Published: August 2010

ABSTRACTThe search for flavonoids with novel therapeutic effects has been intense. Wogonin, as a naturally existing monoflavonoid, has been shown to have therapeutic potentialin vitroandin vivo.Methods for its extraction from herbs and its chemical synthesis have been developed. Pharmacokinetic studies have shown a rapid tissue distribution and prolonged plasma elimination phase of wogonin. It has been shown experimentally that wogonin exerts anti‐oxidant activity, which may, in part, underlie its antiinflammatory, anti‐cancer, antiviral and neuroprotective actions. The recent discovery of its anxiolytic activity suggests a new mechanism of action, involving interaction with the benzodiazepine (BZD) binding site of the GABAAreceptor and modulation of this receptor activity. Although the safety record of wogonin is remarkable and voluminous literature about its pharmacological effects is available, it has not been used in Western medicine in the form of a pure chemical. In this article we review its therapeutic effects, its sources and pharmacokinetic profile to highlight its therapeutic potential.
Latin America and the Dollar Bloc in the Twenty-first Century: To Dollarize or Not?
Authors: Jameson Kenneth P. 
Published: August 2010

AbstractThe choice of exchange rate regime is a continuing challenge to Latin American policymakers, who currently face pressure to dollarize their economies. The constraints imposed by the “dollar bloc,” the informal but powerful currency bloc that ties Latin America to the dominant currency, are central to that choice. Current weak economic performance has called the bloc's norms and principles into question and has made the exchange rate an open issue. Ecuador's full official dollarization is one possible strategy for countries with political stability but poor economic performance to gain access to needed dollar resources. Most of Latin America, however, will continue with variants of managed floating exchange rates, and the periodic foreign exchange crises will provide access to official dollar resources and facilitate renegotiation of the terms of outstanding debt.
Cuba: From “Dollarization” to “Euroization” or “Peso Reconsolidation”?
Authors: Ritter Archibald R. M. , Rowe Nicholas 
Published: August 2010

AbstractSince its “depenalization” in 1993, the U.S. dollar has become possibly a more significant component of Cuba's money supply than the old peso. What are the alternatives? The euro seems inappropriate, given the inevitability of eventual normalization of relations with the United States. More advantageous would be to restore the Cuban peso, though this would involve unifying the bifurcated economic structure and the dual monetary and exchange rate systems. The Cuban government has yet to announce its plans. This study argues that an appropriate mix of exchange rate, monetary, fiscal, and income or wage and salary policies should support a rehabilitation of the Cuban peso.
Revolution or Contribution? Rational Choice Approaches in the Study of Latin American Politics
Authors: Huber Evelyne , Dion Michelle 
Published: August 2010

AbstractThis article assesses the contributions of studies in the rational choice (RC) tradition to scholarly understanding of Latin American politics. It groups some representative works according to their use of RC assumptions, and also reviews some of the major works in the institutionalist tradition. It argues that works in the RC tradition have neither forced a major rethinking of established theories nor filled major lacunae, although they have illuminated some phenomena that were only partly understood. The RC approach works best for narrow questions in which power relations and structural constraints are stable, whereas its essential assumptions become untenable in questions that involve shifting power relations among social groups and the state over time.
The Uneven Performance of Third Wave Democracies: Electoral Politics and the Imperfect Rule of Law in Latin America
Authors: Foweraker Joe , Krznaric Roman 
Published: August 2010

AbstractThis article investigates the performance of the new democracies of the third wave by developing a conceptual model of the core elements of liberal democratic government and by constructing a new Database of Liberal Democratic Performance. The performance is shown to be uneven in two main ways. First, the institutional attributes of democratic government advance while individual and minority rights languish. Second, particular institutional attributes coexist uncomfortably, as do particular rights. A comparison of Brazil, Colombia, and Guatemala complements the big picture drawn from the database and focuses on the specific contextual conditions that can create the general political contours of the wave. The uneven democratic performance of these cases is mainly explained by the combination of persistent oligarchic power and a largely unaccountable military. Yet uneven performance, and the imperfect rule of law in particular, does not necessarily prevent democratic survival.
Breaking out is Hard to Do: Exit, Voice, and Loyalty in Mexico's One-Party Hegemonic Regime
Authors: Langston Joy 
Published: August 2010

Abstract
Theoretically based on Albert O. Hirschman's Exit, Voice, and Loyalty, this study examines three cases of rupture or exit by Mexican presidential contenders, in 1940, 1952, and 1988, and one “noncase,” in 1999, with a view to how dissidents' strategies shape political institutions. Mexico's PRI-dominated political system depended on its leaders' ability to create an equilibrium based on mutual incentives to remain loyal to the regime.
The European Union and Democracy in Latin America
Authors: Youngs Richard 
Published: August 2010

Abstract
The European Union has developed a significant range of democracy promotion initiatives in Latin America since the 1990s. The E.U.'s approach to democracy building has been seen to possess a number of strengths relative to U.S. policy, especially in connection with grassroots developmental imperatives. European policy itself, however, has a number of limitations. It has inadequately conceptualized the linkages between economic and political dimensions; it has insufficiently recognized the potential benefits of balancing bottom-up and top-down approaches. The E.U.'s influence over Latin American governments has remained more nebulous than that of the United States. European and U.S. policies in Latin America have both rivaled and complemented each other. Understanding this might inform both actors' democracy promotion efforts in the region.
Institutional Change and Ethnic Parties in South America
Authors: Van Cott Donna Lee 
Published: August 2010

AbstractThe central question of this article is why indigenous social movements formed electorally viable political parties in Latin America in the 1990s. This development represents a new phenomenon in Latin America, where ethnic parties have been both rare and unpopular among voters. Institutional reforms in six South American countries are examined to see if the creation and success of these parties can be correlated with changes in electoral systems, political party registration requirements, or the administrative structure of the state. The study concludes that institutional change is likely to be a necessary but not sufficient condition for the emergence and electoral viability of ethnic parties.
What Macroeconomic Measures Are Needed for Free Trade to Flourish in the Western Hemisphere?
Authors: Eichengreen Barry 
Published: August 2010

AbstractRecent experience has made clear the importance of macroeconomic stability, and exchange rate stability in particular, in generating support for regional integration. The tensions created by exchange-rate and financial volatility are clearly evident in the recent history of Mercosur and may also hinder the development of a Free Trade Area of the Americas. This essay argues that ambitious schemes for a single regional currency are not a practical response to this problem. Nor would a system of currency pegs or bands be sufficiently durable to provide a lasting solution. Instead, countries must solve this problem at home. In practice, this means adopting sound and stable monetary policies backed by a clear and coherent operating strategy, such as inflation targeting. With such policies in place, exchange rate volatility can be reduced to levels compatible with regional integration.
Horizontal Accountability in Transitional Democracies: The Human Rights Ombudsman in El Salvador and Guatemala
Authors: Dodson Michael , Jackson Donald 
Published: August 2010

AbstractPostwar El Salvador and Guatemala have undertaken to reform and democratize the state and to support the rule of law. Each country entered the 1990s hobbled by a legacy of authoritarian rule, while a corrupt and politicized judiciary offered virtually no check on the abuse of power. Because the judiciary has performed poorly as an institution of horizontal accountability, this article examines the performance of a new “accountability agency,” the Human Rights Ombudsman. The article discusses the context in which the office was established and developed in each country, perceptions of its performance, and political responses as the office began to perform its function of holding public officials accountable in their exercise of power. Unfortunately, this new office may fall prey to the same weaknesses that have plagued older institutions in both countries.
Business Versus Business?Gruposand Organized Business in Colombia
Authors: Rettberg Angelika 
Published: August 2010

AbstractThis article examines business political behavior in Colombia during the scandal-ridden presidency of Ernesto Samper (1994-98), highlighting the mechanisms by whichgrupos(diversified economic groups) undermined the ability of organized business to present collective political positions. Evidence that the presidential campaign had been funded by drug traffickers prompted business associations to demand Samper's resignation. Butgrupos, the firms of which are affiliated with associations, supported the president. This division weakened the position of organized business regarding the resignation, as well as its own political legitimacy. This study argues thatgruposface strong incentives to act outside business associations to advance their particular interests. Scholars assessing the strength of organized business in Latin America will increasingly encounter the impact of grupos on business institutional responses to policy.
Electoral Competition and the New Party System in Mexico
Authors: Klesner Joseph L. 
Published: August 2010

Abstract
Mexico's former opposition parties had specific social bases that would not, on their own, have catapulted either opposition party into power. In the 1990s, specific regional bases of support developed for the parties, reflecting their efforts to develop their organizations more locally. Nationally, this led to the emergence of two parallel two-party systems, PAN-PRI competition in the north and center-west and PRD-PRI competition in the south. In parallel, a proregime-antiregime cleavage came to dominate the Mexican party system, which, combined with local-level opposition efforts to oust the PRI, created new incentives for the opposition parties to abandon past emphases on ideological differences and to act like catch-all parties instead. The regime cleavage fostered the dealignment of the Mexican electorate, a process that promoted the development of catch-all parties. Movement within the parties to behave like catch-all parties has not come without internal tensions, but electoral dynamics prove powerful inducements to catch-all behavior.
Bolivia: Another Uncompleted Revolution
Authors: Barr Robert R. 
Published: August 2010

AbstractSince 1999, growing citizen dissatisfaction in Bolivia has been manifest in a cycle of often violent protests. Citizens believe that they have no means of expressing themselves except demonstrations. The public has grown weary of neoliberalism, which is perceived as benefiting only the elite. A recent economic downturn provided the catalyst for the unrest. Underlying these economic concerns, however, are fundamental problems with representation. The second Bolivian “revolution” involved not only the shift from state-led economic development to neoliberalism but also a shift from corporatism to pluralism. Representative institutions have not fully responded to the new pluralistic landscape, despite a range of political reforms. Many Bolivians find that their voice in government has weakened even as their needs have grown. The Bolivian case thereby highlights the obstacles young democracies face in winning over decreasingly tolerant citizens.
The Lost Sexenio: Vicente Fox and the New Politics of Economic Reform in Mexico
Authors: Pastor Manuel , Wise Carol 
Published: August 2010

AbstractThe 2000 presidential election of opposition candidate Vicente Fox signaled an end to seven decades of Mexico's single-party regime and seemed to herald the advent of truly competitive politics. But by 2003, economic reform had largely stalled, and Fox's party suffered a historically unprecedented midterm loss in the congress. This article analyzes the underpinnings of policy gridlock in the Fox administration. Fox inherited the need for microeconomic restructuring and increased competitiveness, more innovative and pragmatic state policies, the need to pay attention to the country's sharp income inequalities, and the challenge of crafting a political strategy that could build a middle ground and foster policy consensus. With his party's minority standing in the congress, Fox was constrained from the start by divided government. But more effective statecraft and coalition building would have helped. These will be essential elements for the success of any post-Fox regime.