Table of Contents

Reviews

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  • Stephen R. Bloom,
  • Francis P. Kuhajda,
  • Ismail Laher,
  • Xavier Pi-Sunyer,
  • Gabriele V. Ronnett,
  • Tricia M.M. Tan,
  • and David S. Weigle

  The Obesity Epidemic: Pharmacological Challenges

  Mol Interv April 2008 8:82-98; doi:10.1124/mi.8.2.6
  • Abstract
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  As obesity claims an increasing number of lives every year, our collective awareness of obesity as a global epidemic has heightened. There are complex origins for this relentless epidemic: easy access to large quantities of inexpensive foods that are calorie-rich; eating habits that have changed to match fast-paced and automated lifestyles; and increasingly sedentary work and recreation. These factors compound inherited tendencies to store excess calories as a defense mechanism for times of famine—the so-called thrifty-gene theory. It is estimated that more than thirty percent of adults, and about fifteen percent of juveniles, are obese. These statistics are accompanied by dramatic increases of diseases such as type 2 diabetes, cardiovascular and respiratory diseases, depression, and some forms of cancer. More than 300,000 obesity-related deaths occur in the US yearly; in fact, the incidence of type 2 diabetes in children has increased by more than tenfold. The urgency of the obesity epidemic has fueled biomedical research into the mechanisms that underlie energy homeostasis and the perturbations of metabolic balances that result in disease. Many of these mechanisms—both peripheral and within the central nervous system—suggest promising avenues for pharmacological intervention into obesity, overweight, and the comorbidities of modern, globalized living. (I. Laher)

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  • P. Jeffrey Conn,
  • Carol Tamminga,
  • Darryle D. Schoepp,
  • and Craig Lindsley

  Schizophrenia: Moving Beyond Monoamine Antagonists

  Mol Interv April 2008 8:99-107; doi:10.1124/mi.8.2.7
  • Abstract
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  Schizophrenia is a disabling psychiatric disorder characterized by positive, negative, and cognitive symptoms. The first pharmacological treatments for schizophrenia were discovered by serendipitous, albeit carefully documented, clinical observations. The discovery of chlorpromazine and other dopamine D₂ receptor antagonists as antipsychotic agents set the early course of drug discovery in the context of schizophrenia and other psychiatric disorders, and various monoamine receptors became the prime focus of neuropharmacological studies. Success in treating the positive symptoms nevertheless remained limited by the general lack of efficacy in addressing negative symptoms and cognitive impairment. In recent years, several new experimental approaches have emerged for the identification and treatment of different symptom clusters that do not rely on blockade of monoamine receptors. Muscarinic, nicotinic, and glutamatergic signaling mechanisms have become essential to neuropharmacological and behavioral models of discrete aspects of schizophrenia. And as a consequence of these insights, novel drug entities have become available to study and potentially treat the disabling cognitive and negative symptoms of psychiatric disease. Current attempts to target a new range of receptors entail unprecedented fine-tuning in the pharmacological manipulation of specific receptor subtypes.