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Journal of Obesity 2011Past therapies for the treatment of obesity have typically involved pharmacological agents usually in combination with a calorie-controlled diet. This paper reviews the...
Past therapies for the treatment of obesity have typically involved pharmacological agents usually in combination with a calorie-controlled diet. This paper reviews the efficacy and safety of pharmacotherapies for obesity focusing on drugs approved for long-term therapy (orlistat), drugs approved for short-term use (amfepramone [diethylpropion], phentermine), recently withdrawn therapies (rimonabant, sibutamine) and drugs evaluated in Phase III studies (taranabant, pramlintide, lorcaserin and tesofensine and combination therapies of topiramate plus phentermine, bupropion plus naltrexone, and bupropion plus zonisamide). No current pharmacotherapy possesses the efficacy needed to produce substantial weight loss in morbidly obese patients. Meta-analyses support a significant though modest loss in bodyweight with a mean weight difference of 4.7 kg (95% CI 4.1 to 5.3 kg) for rimonabant, 4.2 kg (95% CI 3.6 to 4.8 kg) for sibutramine and 2.9 kg (95% CI 2.5 to 3.2 kg) for orlistat compared to placebo at ≥12 months. Of the Phase III pharmacotherapies, lorcaserin, taranabant, topiramate and bupropion with naltrexone have demonstrated significant weight loss compared to placebo at ≥12 months. Some pharmacotherapies have also demonstrated clinical benefits. Further studies are required in some populations such as younger and older people whilst the long term safety continues to be a major consideration and has led to the withdrawal of several drugs.
PubMed: 21197148
DOI: 10.1155/2011/179674 -
Pharmacotherapy Dec 2013To examine national trends in prescription antiobesity drug use in the United States.
STUDY OBJECTIVE
To examine national trends in prescription antiobesity drug use in the United States.
DESIGN
Data analysis.
DATA SOURCE
The IMS Health Vector One National and Total Patient Tracker and Encuity Research Treatment Answers databases, the Source Healthcare Analytics Source Lx database, and IMS LifeLink database.
MEASUREMENTS AND MAIN RESULTS
National drug use estimates from 1991-2011 were extracted from the IMS Health Vector One National database, and patient characteristics from 2008-2011 were extracted from the Vector One Total Patient Tracker and Encuity Research Treatment Answers databases. The Source Healthcare Analytics Source Lx database was used to examine duration of antiobesity drug use from 2002-2011, with a sensitivity analysis performed using the IMS LifeLink database. In 2011, approximately 2.74 million patients used antiobesity drugs, predominantly phentermine (2.43 million patients). The use of prescription orlistat and sibutramine was relatively uncommon. Eighty-five percent of antiobesity drug users were female, 62% were aged 17-44 years, and 4.5% had a body mass index of ≤ 24.9 kg/m(2) . Duration of use was generally short and most patients only had one episode of antiobesity drug use during the observation period. The longest episode of use was 30 days or less in 47-58% of patients. Approximately one quarter of the patients used antiobesity drugs for longer than 90 days, including phentermine and other amphetamine congeners whose labels recommend short-term use, not exceeding "a few weeks." Only 1.3-4.2% of antiobesity drug users used them for longer than 1 year. Concomitant use of two or more prescription weight-loss drugs was generally uncommon, although phentermine was dispensed during 13-16% of benzphetamine, diethylpropion, or phendimetrazine episodes of use.
CONCLUSION
Phentermine dominated the prescription weight-loss market. Despite the indication of short-term use for amphetamine congeners, duration of use was similar to other antiobesity drugs. Nevertheless, the reasons for and implications of the limited duration of use observed with all prescription antiobesity drugs deserve further investigation.
Topics: Adolescent; Adult; Anti-Obesity Agents; Child; Child, Preschool; Databases, Factual; Female; Humans; Infant; Male; Middle Aged; Obesity; Practice Patterns, Physicians'; Time Factors; United States; Weight Loss; Young Adult
PubMed: 24019195
DOI: 10.1002/phar.1342 -
Scientific Reports Nov 2019Amfepramone (AFP) is an appetite-suppressant drug used in the treatment of obesity. Nonetheless, studies on interindividual pharmacokinetic variability and its... (Randomized Controlled Trial)
Randomized Controlled Trial
Amfepramone (AFP) is an appetite-suppressant drug used in the treatment of obesity. Nonetheless, studies on interindividual pharmacokinetic variability and its association with genetic variants are limited. We employed a pharmacokinetic and pharmacogenetic approach to determine possible metabolic phenotypes of AFP and identify genetic markers that could affect the pharmacokinetic variability in a Mexican population. A controlled, randomized, crossover, single-blind, two-treatment, two-period, and two sequence clinical study of AFP (a single 75 mg dose) was conducted in 36 healthy Mexican volunteers who fulfilled the study requirements. Amfepramone plasma levels were measured using high-performance liquid chromatography mass spectrometry. Genotyping was performed using real-time PCR with TaqMan probes. Four AFP metabolizer phenotypes were found in our population: slow, normal, intermediate, and fast. Additionally, two gene polymorphisms, ABCB1-rs1045642 and CYP3A4-rs2242480, had a significant effect on AFP pharmacokinetics (P < 0.05) and were the predictor factors in a log-linear regression model. The ABCB1 and CYP3A4 gene polymorphisms were associated with a fast metabolizer phenotype. These results suggest that metabolism of AFP in the Mexican population is variable. In addition, the genetic variants ABCB1-rs1045642 and CYP3A4-rs2242480 may partially explain the AFP pharmacokinetic variability.
Topics: ATP Binding Cassette Transporter, Subfamily B; Adult; Appetite Depressants; Cytochrome P-450 CYP3A; Diethylpropion; Female; Humans; Male; Metabolic Clearance Rate; Middle Aged; Pharmacogenomic Variants; Polymorphism, Single Nucleotide
PubMed: 31780765
DOI: 10.1038/s41598-019-54436-z -
British Medical Journal Aug 1962
Topics: Appetite; Behavior, Addictive; Diethylpropion; Propiophenones; Substance-Related Disorders; Sympathomimetics
PubMed: 13879863
DOI: 10.1136/bmj.2.5302.456 -
Canadian Medical Association Journal May 1963
Topics: Appetite Depressants; Diethylpropion; Humans; Substance-Related Disorders
PubMed: 14018413
DOI: No ID Found -
British Journal of Pharmacology and... Jun 1967
Clinical Trial Comparative Study Randomized Controlled Trial
Topics: Adult; Appetite Depressants; Chlorphentermine; Clinical Trials as Topic; Diethylpropion; Female; Flicker Fusion; Humans; Male; Phenmetrazine
PubMed: 5341005
DOI: 10.1111/j.1476-5381.1967.tb02137.x -
Brazilian Journal of Medical and... May 2013Neonatal handling induces several behavioral and neurochemical alterations in pups, including decreased responses to stress and reduced fear in new environments....
Neonatal handling induces several behavioral and neurochemical alterations in pups, including decreased responses to stress and reduced fear in new environments. However, there are few reports in the literature concerning the behavioral effects of this neonatal intervention on the dams during the postpartum period. Therefore, the aim of the current study was to determine if brief postpartum separation from pups has a persistent impact on the dam's stress response and behavior. Litters were divided into two neonatal groups: 1) non-handled and 2) handled [10 min/day, from postnatal day (PND) 1 to 10]. Weaning occurred at PND 21 when behavioral tasks started to be applied to the dams, including sweet food ingestion (PND 21), forced swimming test (PND 28), and locomotor response to a psychostimulant (PND 28). On postpartum day 40, plasma was collected at baseline for leptin assays and after 1 h of restraint for corticosterone assay. Regarding sweet food consumption, behavior during the forced swimming test or plasma leptin levels did not differ between dams briefly separated and non-separated from their pups during the postpartum period. On the other hand, both increased locomotion in response to diethylpropion and increased corticosterone secretion in response to acute stress were detected in dams briefly separated from their pups during the first 10 postnatal days. Taken together, these findings suggest that brief, repeated separations from the pups during the neonatal period persistently impact the behavior and induce signs of dopaminergic sensitization in the dam.
Topics: Animals; Animals, Newborn; Corticosterone; Female; Humans; Leptin; Male; Maternal Deprivation; Motor Activity; Pregnancy; Rats, Wistar; Stress, Psychological; Swimming; Time Factors
PubMed: 23739746
DOI: 10.1590/1414-431X20132784 -
Brazilian Journal of Medical and... Jun 2015Amfepramone (diethylpropion) is an appetite-suppressant drug used for the treatment of overweight and obesity. It has been suggested that the systemic and central...
Amfepramone (diethylpropion) is an appetite-suppressant drug used for the treatment of overweight and obesity. It has been suggested that the systemic and central activity of amfepramone produces cardiovascular effects such as transient ischemic attacks and primary pulmonary hypertension. However, it is not known whether amfepramone produces immediate vascular effects when applied in vitro to rat aortic rings and, if so, what mechanisms may be involved. We analyzed the effect of amfepramone on phenylephrine-precontracted rat aortic rings with or without endothelium and the influence of inhibitors or blockers on this effect. Amfepramone produced a concentration-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings that was not affected by the vehicle, atropine, 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. The vasorelaxant effect of amfepramone was significantly attenuated by NG-nitro-L-arginine methyl ester (L-NAME) and tetraethylammonium (TEA), and was blocked by removal of the vascular endothelium. These results suggest that amfepramone had a direct vasorelaxant effect on phenylephrine-precontracted rat aortic rings, and that inhibition of endothelial nitric oxide synthase and the opening of Ca2+-activated K+ channels were involved in this effect.
Topics: Acetylcholine; Animals; Aorta, Thoracic; Appetite Depressants; Calcium Channels; Diethylpropion; Endothelium, Vascular; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase Type III; Phenylephrine; Potassium Channels; Rats, Wistar; Tetraethylammonium; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents
PubMed: 25831200
DOI: 10.1590/1414-431X20144261 -
American Family Physician Apr 2011
Topics: Appetite Depressants; Cardiovascular Diseases; Chemotherapy, Adjuvant; Diethylpropion; Evidence-Based Practice; Exercise; Feeding Behavior; Humans; Obesity; Pharmacovigilance; Phentermine; Treatment Outcome; Weight Loss; Weight Reduction Programs
PubMed: 21674993
DOI: No ID Found -
Pharmacology, Biochemistry, and Behavior Aug 1987Four commonly used anorectics which are amphetamine analogues were tested for their action on responsiveness in an acoustic startle test when rats were given daily IP...
Four commonly used anorectics which are amphetamine analogues were tested for their action on responsiveness in an acoustic startle test when rats were given daily IP injections adequate to produce a change in body weight. Drugs were given for 22 days. None of these drugs increased startle responsiveness as does the amphetamine parent compound. Instead, fenfluramine and phenylpropanolamine decreased startle responsiveness and phentermine and diethylpropion produced no change. There was no relationship between drug action and body weight. Partial tolerance was found for the fenfluramine action on startle and complete tolerance was found for its action on body weight gain. The fenfluramine action is compatible with the extensive literature on humans and animals indicating sedative properties.
Topics: Acoustic Stimulation; Animals; Appetite Depressants; Body Weight; Diethylpropion; Drug Tolerance; Fenfluramine; Male; Phentermine; Phenylpropanolamine; Rats; Reflex, Startle
PubMed: 3659098
DOI: 10.1016/0091-3057(87)90203-6