Disease relevance of Phentermine hydrochloride

• Psychological treatment of obesity with phentermine resin as an adjunct [1].
• CONCLUSION: In a population-based sample, use of fenfluramine or dexfenfluramine, alone or in combination with phentermine, was associated with aortic regurgitation independent of aortic dilatation or fibrocalcification [2].
• We therefore initiated a 2-year placebo-controlled trial of the weight-loss medications fenfluramine and phentermine in type 2 diabetic subjects [3].
• RESEARCH DESIGN AND METHODS: A total of 44 overweight (> 120% ideal body weight) subjects with type 2 diabetes were enrolled in a randomized, placebo-controlled, double-blind trial of fenfluramine and phentermine [3].
• Valvular heart disease in fenfluramine- phentermine-treated patients: a comparison with control patients [4].

Psychiatry related information on Phentermine hydrochloride

• To assess continued efficacy of anorexiants after 3 years of use, 52 participants (43% of those starting) entered a second double-blind trial to compare 60 mg sustained-release fenfluramine plus 15 mg phentermine resin versus placebo added to behavior modification, caloric restriction, and exercise [5].
• Pharmacotherapy for the management of obesity is primarily aimed at weight loss, weight loss maintenance and risk reduction, and has included thyroid hormone, amphetamines, phentermine, amfepramone (diethylpropion), phenylpropanolamine, mazindol, fenfluramines and, more recently, sibutramine and orlistat [6].
• Recent clinical reports indicate that combined administration of phentermine and fenfluramine may have useful effects in the treatment of drug abuse [7].
• Smoking cessation in a patient being treated with fenfluramine plus phentermine for simple obesity [8].
• Alterations in alcohol consumption, withdrawal seizures, and monoamine transmission in rats treated with phentermine and 5-hydroxy-L-tryptophan [9].

High impact information on Phentermine hydrochloride

• BACKGROUND: Recent case reports suggest that a combination of the appetite suppressants fenfluramine and phentermine is associated with an increased risk of cardiac-valve regurgitation [10].
• BACKGROUND: Fenfluramine and phentermine have been individually approved as anorectic agents by the Food and Drug Administration (FDA) [11].
• Compared to controls fed at libitum, reductions in food intake were for phentermine, 7%; fenfluramine, 17%; diethylpropion, 17%, whereas reduction in body lipid content were for phentermine, 16%; mazindol, 18%; fenfluramine, 8%; diethylpropion, 10% [12].
• Since diet restriction by 22% (in the absence of treatment with any drug) resulted in a body lipid content 12% below that of controls fed ad libitum, these results suggest that some of the lipid loss caused by phentermine and possibly mazindol is due to increased energy expenditure [12].
• Completion rates varied from 52.8% of phentermine recipients in a 9-month study, to 40% of fenfluramine recipients in a 24-week comparative study with phentermine and 18% of amfepramone recipients in a 24-week study [6].

Chemical compound and disease context of Phentermine hydrochloride

• Expert readers blinded to current therapy read echocardiograms centrally at Cornell Medical Center. Analyses of the associations between use of fenfluramine/dexfenfluramine (alone or with phentermine) and aortic regurgitation adjusted for potential confounders, including aortic root dilatation and valve fibrocalcification [2].
• Following a 9-h withdrawal period from the alcohol-containing diet, phentermine enhanced the effects of 5-HTP on both reduction of alcohol withdrawal seizures as well as changes in striatal serotonin [9].
• Phentermine, in combination with fluoxetine, produced greater reductions in food intake and body weight than phentermine alone [13].
• Drug discrimination studies were conducted in six male Sprague-Dawley rats trained to discriminate the interoceptive cues produced by 10 mg/kg cocaine in an effort to investigate if there is stimulus generalization to phentermine or phentermine + fenfluramine [14].
• RESULTS: There are several pharmacological options currently available for the treatment of overweight and obese individuals in the United States, including phentermine, sibutramine, and orlistat, with only sibutramine and orlistat being indicated for use in the long term (> 6 months) [15].

Biological context of Phentermine hydrochloride

• Pregnant rats were infused with phentermine plus dexfenfluramine from days 3 through 17 of gestation [16].
• This study was a detailed medical record review of 18 previously reported users of fenfluramine and phentermine, all with valve abnormalities on echocardiogram and 2 with surgical pathology [17].
• The synergism between fenfluramine and phentermine highlights the need to more completely understand the pharmacology and neurochemistry of appetite suppressants prior to use in combination pharmacotherapy for the treatment of obesity [18].
• CONCLUSIONS: Treatment with phentermine reduces caloric intake slightly less than is commonly observed in CR studies [19].
• Pregnancy outcomes after first trimester exposure to phentermine/fenfluramine [20].

Anatomical context of Phentermine hydrochloride

• There were no cases of idiopathic cardiac-valve abnormalities among the subjects who had not taken appetite suppressants or among those who took only phentermine [10].
• The N-hydroxylation of phentermine by rat liver microsomes [21].
• (+)-Amphetamine, (+/-)-ephedrine, and phentermine are commonly used appetite suppressants that release monoamines from nerve cells by acting as substrates for biogenic amine transporters [22].
• This oxidation accounts for differences noted in levels of N-hydroxyphentermine formed from phentermine in washed and unwashed microsome preparations [23].
• Effects on serotonin in rat hypothalamus of D-fenfluramine, aminorex, phentermine and fluoxetine [24].

Associations of Phentermine hydrochloride with other chemical compounds

• Treatment of a 4-year-old boy with ADHD with the dopamine releaser phentermine [25].
• Appetite suppressant drugs as inhibitors of human cytochromes P450: in vitro inhibition of P450-2D6 by D- and L-fenfluramine, but not phentermine [26].
• The 5-HT releaser fenfluramine attenuated methamphetamine self-administration to a much larger extent than phentermine (to 37% of baseline responding) at a dose of 1.8 mg/kg that did not generalize to methamphetamine and did not decrease rate of responding in the discrimination study [27].
• Clinical case studies suggest that combined administration of the serotonergic agent fenfluramine (FEN) and the weak amphetamine-like anorexic agent phentermine (PHEN) may be useful in the treatment of alcohol and cocaine addictions [28].
• The 10-fold difference in the size of the SEP for compounds known to induce pulmonary phospholipidosis (chlorphentermine and IMIP) and known not to induce lipidosis (phentermine and amphetamine) may suggest a possible involvement of the SEP in the onset of phospholipidosis; this possibility is discussed [29].

Gene context of Phentermine hydrochloride

• These data suggest that phentermine inhibition of human MAO A (or of MAO B) is too weak to be of pharmacological relevance [30].
• Phentermine was also observed to be a competitive inhibitor of recombinant human liver MAO B with a K(I) value of 375+/-42 microM, a value similar to that observed with the rat enzyme (310-416 microM) [30].
• Phentermine inhibited serotonin-metabolizing (MAO-A) activity in all three tissues with K(i) values of 85-88 microM [31].
• The purpose of the present work was to examine the effect of phentermine coadministration on fenfluramine-induced depletion of 5-HT in mouse forebrain [32].
• Autopsy findings of heart and lungs in a patient with primary pulmonary hypertension associated with use of fenfluramine and phentermine [33].

Analytical, diagnostic and therapeutic context of Phentermine hydrochloride

• Long-term weight control study. I (weeks 0 to 34). The enhancement of behavior modification, caloric restriction, and exercise by fenfluramine plus phentermine versus placebo [34].
• On visual analog scales, participants rated fenfluramine plus phentermine as more helpful than placebo (50.3 +/- 0.5 versus 20.3 +/- 0.3) and not bothersome (fenfluramine plus phentermine, 17.4 +/- 0.3 versus 13.5 +/- 0.2) [34].
• In the present experiment graded doses of phentermine, an anorectic similar to amphetamine in structure and mechanism of action, were made available to naive free-feeding (FF) or 80% free-feeding weight (FFW) rats for IV self-administration [35].
• Twenty-six women with a mean (+/- SD) age of 47.0 +/- 7.2 years, weight of 97.6 +/- 13.0 kg, and body mass index of 36.5 +/- 5.0 kg/m2 were prescribed 60 mg/d of fenfluramine and 15 mg/d of phentermine for one year [36].
• Gas-liquid chromatographic determination of phentermine in human plasma following oral administration to healthy subjects [37].

References