Clinical Psychopharmacology of Amphetamine and Related Compounds
John Caldwell, S. Joseph Mulé in Amphetamines and Related Stimulants: Chemical, Biological, Clinical, and Sociological Aspects, 2019
Although others had previously remarked on the suppression of appetite experienced by patients who had taken amphetamine, Davidoff and Reifenstein6 were the first to suggest that the drug’s anorectic activity might be of potential clinical use in the management of obesity. Direct measurement of such an anorectic action in man was not attempted for some 10 years after the drug had been successfully introduced clinically. Harris and colleagues39 demonstrated that amphetamine significantly reduced food intake, but they did not attempt to evaluate its effect on hunger itself. Shortly afterwards, however, Janowitz and Grossman40 reported that 10 mg dextroamphetamine taken orally 1 hr before lunch “abolished all hunger sensations and markedly depressed the desire to eat … in all instances”. Others reported that the maximum anorectic effect occurred some 2 to 3 hr after administration, but, contrary to the findings of Janowitz and Grossman, they noted a wide intersubject variation,41 with only 20% responding markedly. Fifteen years earlier, Bahnsen et al.7 had remarked that a similar proportion of normal subjects experienced an anorectic effect; this was, however, four times as many as those who experienced a similar effect after placebo.
Synthetic Cathinones and Related Fatalities in the United Kingdom
Ornella Corazza, Andres Roman-Urrestarazu in Handbook of Novel Psychoactive Substances, 2018
Some synthetic cathinones remain licenced for medicinal use. For instance, bupropion (Amfebutamone, Zyban, Wellbutrin), which is primarily used as an antidepressant and a smoking cessation aid, has also been used for recreational purposes because of its cocaine-like effects (McCormick, 2002; Vento et al., 2013). Pyrovalerone, structurally related to MDPV, because of its stimulant effects, has been used in the clinical treatment of lethargy and chronic fatigue (Gardos & Cole, 1971). It has also been employed as an appetite suppressant and anorectic in France and elsewhere. However, problems with abuse and dependence mean it has not often been prescribed in recent years (Deniker, Lôo, Cuche, & Roux, 1975). Pyrovalerone is covered by Schedule IV of the United Nations (UN) 1971 Convention on Psychotropic Substances. In the UK, it was controlled as a Class C drug under the Misuse of Drugs Act 1971, prior to the inclusion of additional cathinones, e.g., mephedrone, in April 2010. Amfepramone was also categorized as a Class C drug.
Type 2 Diabetes in Childhood
Emmanuel C. Opara, Sam Dagogo-Jack in Nutrition and Diabetes, 2019
The most common types of prescription weight loss medications are appetite-suppressing anorectic agents, and include phentermine, phendimetrazine, methamphetamine, benzphetamine, and diethylpropion. These are categorized by the FDA as controlled dangerous substances (CDS). They are only approved for short-term use due to their potential for overuse and abuse. Although cleared by the FDA, they are contraindicated in subjects with cardiac disease, hypertension, or hyperthyroidism. Side effects include increased blood pressure, tachycardia, anxiety, restlessness, dry mouth, and constipation. None of these medications is FDA-approved for use in those younger than 18 years, though some have used them in patients as young as 12 years [57].
Differential effects of citalopram on the intake of high fat or high carbohydrates diets in female and male rats
Published in Nutritional Neuroscience, 2021
Amparo L. De la Fuente-Reynoso, Eliana Barrios De Tomasi, Jorge Juárez
There are discrepancies in the literature related to the effect produced by the increase in serotonin availability on carbohydrate or fat consumption, especially when these substances are available simultaneously. Several experiments have addressed the issue of whether the anorectic effects of SSRIs are due to a general decrease in energy intake, or are specific to certain macronutrients [16, 17]. In this regard, after injections of SSRI, suppressed carbohydrate intake was observed, but with no effect on either fat or protein intake. This suggests a role for serotonin in regulating carbohydrate intake [18, 19]. In contrast, Blundell et al. [20] found that the most pronounced effect of serotonin was reducing fat intake in rats exposed to various high-fat diets. In another study, female Long-Evans rats treated with either single injections of fluoxetine (5.0, 10.0, 20.0 mg/kg, i.p.) or chronic daily treatment with this SSRI (10 mg/kg for 28 days) significantly reduced their total caloric intake compared to a group treated with a vehicle. Moreover, fluoxetine significantly suppressed fat and protein intake, but not carbohydrate intake, after both acute and chronic administration [21]. In addition, administration of 1 mg/kg of WAY163909 (a 5-HT2C receptor agonist) significantly suppressed the binge intake of high-fat foods in rodents, suggesting that 5-HT2CR activation may offer a viable therapeutic approach to suppressing binge-eating episodes in humans [22]. In any case, controversy continues to exist as to whether serotonin’s effects are specific for carbohydrate or fat intake [23].
The risk of cardiovascular complications with current obesity drugs
Published in Expert Opinion on Drug Safety, 2020
Ariana M. Chao, Thomas A. Wadden, Robert I. Berkowitz, Kerry Quigley, Frank Silvestry
Phentermine and topiramate were both approved by the FDA as individual medications prior to the approval of the combined product for chronic weight management in 2012. Phentermine is a sympathomimetic amine anorectic that was approved in 1959 for short-term (<3 months) treatment of obesity[27]. Topiramate is an anti-epileptic medication that modifies voltage-gate sodium and calcium channels and targets gamma-aminobutyric acid-mediated pathways[28]. Topiramate is approved for the treatment of epilepsy and migraine prophylaxis. The exact mechanism of action for weight loss is not known. The fixed-dose combination medication is started at a dose of 3.75 mg of phentermine and 23 mg of topiramate ER, once daily in the morning, and titrated to a recommended dose of 7.5 mg/46 mg[29]. The dose can be further increased to 15 mg/92 mg if 3% weight loss is not achieved after 12 weeks. The medication should be discontinued after 12 weeks if a 5% weight loss is not achieved after reaching 15 mg/92 mg.
The limits and challenges of antiobesity pharmacotherapy
Published in Expert Opinion on Pharmacotherapy, 2020
Kishore M Gadde, Katelyn D Atkins
In 1947, the US Food and Drug Administration (FDA) approved two branded products of desoxyephedrine (Desoxyn, Hydrin), an amphetamine, as ‘adjuncts to the dietary management of obesity’ based on an article that reported no blood pressure (BP) elevations or evidence of addiction among 110 obese patients treated with the drug [9]. Between 1956 and 1960, five amphetamine congeners were also approved [Table 1] based on safety evaluation only. In 1970, the FDA required that the manufacturers of these already marketed drugs conduct well-controlled studies and submit evidence of efficacy within a year. This ‘Amphetamine Anorectic Drug Project’ involved clinical trials that ranged in duration from 3 weeks to 6 months, mostly around 12 weeks. In the mid-70s, lacking expert consensus on what constituted clinically significant weight loss and how to determine benefit-to-risk balance, the FDA reaffirmed the approval of the previously approved amphetamines and amphetamine congeners based on a crude meta-analysis that revealed ‘trivial,’ but statistically superior weight loss relative to placebo. However, lacking adequate data on addiction potential, the FDA arbitrarily restricted their use for short-term (a few weeks) [9]. This restriction led to a fall in the use of anorectic drugs until publication of a single placebo-controlled study of 121 obese patients (less than one-third completed the study) treated with phentermine plus fenfluramine (Phen-Fen) for up to 4 years [10] led to a steep rise in their prescriptions in the mid-1990s [11].
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