Wilding Pharmacotherapy of Obesity

1. Auflage 2008
ISBN: 978-3-7643-7425-9
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 120 Seiten, eBook

Reihe: Milestones in Drug Therapy

Obesity has become a major epidemic that now rivals smoking as a risk to public health. The ensuing epidemics of diabetes, vascular disease and other complications are set to overwhelm the healthcare systems of wealthy and poorer nations alike. The need for effective pharmacotherapy has never been greater. This book takes a new look at the many potential targets for drug development for regulation of body weight, placing them in the context of the chequered history of drug development for obesity and currently available therapies.Potential peripheral and central nervous system targets are discussed in detail by authors with extensive knowledge and research experience in the science of body weight regulation, and its translation into effective therapies that will benefit patients. This book is of interest to clinicians, researchers in the field and members of the pharmaceutical industry who are interested in learning more about the current state of the art and future directions in the pharmacotherapy of obesity.

Zielgruppe

Research

Autoren/Hrsg.

Wilding, John P. H.

Inhaltsverzeichnis

Why drugs?.- Some historical aspects of drug treatment for obesity.- Regulation of energy balance — towards rational drug design in obesity.- Intestinal lipase inhibitors.- Sibutramine.- The endocannabinoid system as a target for obesity treatment.- Using the body’s natural signals — gut hormones.- Influencing energy expenditure and substrate utilisation.

Leseproben

The endocannabinoid system as a target for obesity treatment (p. 69-70)

Muhammad Khan and John P.H. Wilding

Diabetes and Endocrinology Clinical Research Group, University Hospital Aintree, Clinical Sciences Centre, 3rd Floor, Lower Lane, Liverpool L9 7AL, UK

Introduction

During the past 30 years the prevalence of obesity has risen substantially in most developed countries. Across the world obesity is becoming one of the most preventable and modifiable metabolic disorders. There is evidence linking obesity to an increased risk of more than 30 medical conditions, raising an appropriate concern that this alarming trend will have major health consequences [1]. Serious conditions such as increased risk of type 2 diabetes mellitus (DM), coronary heart disease, hypertension, obstructive sleep apnoea and cancer, higher overall mortality rate and decreased lifespan have been associated with obesity [2, 3]. Morbid obesity can cause a decrease in life expectancy among young adults by as much as 5–20 years [4]. In addition to being a chief health concern, obesity is also becoming a major economic problem with significant consequences for health services worldwide. During the last 20 years beneficial trends have been evident in many cardiovascular disease risk factors including smoking, relative saturated fat intakes and cholesterol levels. Unfortunately, the parallel increase in adverse factors such as increased energy density of foods and reduced exercise, resulting in obesity, has counterbalanced or may have overwhelmed these benefits causing a growing prevalence of obesity-associated cardiometabolic disease [5].

The awareness of the health consequences of overweight and obesity, the benefits of modest weight loss and the frequent failure of lifestyle interventions for both weight loss and weight loss maintenance has led to the search for effective anti-obesity treatment. Evidence suggests that most obese individuals have an inappropriate control of their food intake rather than a metabolic defect in energy expenditure. This concept has turned attention toward drugs which reduce appetite or enhance satiety and so decrease energy intake as compared to thermoregulatory agents which increase energy expenditure.

The endocannabinoid system

Since the discovery of the first cannabinoid receptor together with its endogenous ligand in the early 1990s, the molecular basis for this novel neuromodulatory system has become better understood. The endocannabinoid system is now known to comprise a range of molecules, synthesised on demand from arachidonic acid precursors that regulate synaptic neurotransmission, together with their associated receptors [6]. This system acts as a neuromodulatory system affecting many physiological functions, not only in the central nervous system (CNS), but also in endocrine, reproductive, gastrointestinal, cardiovascular and immune systems. There are now known to be two types of endocannabinoid receptors, known as CB1 and CB2. Their natural ligands were identified as anandamide, monoacyl glycerol, 2-arachidonylglycerol and other fatty acid ethanolamides. The two most extensively studied endocannabinoids are anandamide and 2-arachidonylglycerol, both are synthesised from arachidonic acid and are lipid in nature. Interestingly, endocannabinoids are produced post-synaptically but act on pre-synaptic release of neurotransmitters, mainly causing inhibition of their release [6].