Ionamin online research references
Obes Res. 1998 Jul;6(4):278-84.
The fen-phen finale: a study of weight loss and valvular heart disease.
Wadden TA, Berkowitz RI, Silvestry F, Vogt RA, St John Sutton MG, Stunkard AJ, Foster GD, Aber JL.
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA.
OBJECTIVE: To assess weight loss, as well as the prevalence of valvular heart disease, in 21 obese women who completed 2 years of treatment by fenfluramine and phentermine (fen-phen) in June 1997. RESEARCH METHODS AND PROCEDURES: Patients were 21 of 22 women who had completed a 1-year, open-label trial of fen-phen combined with lifestyle modification. This study describes the results of a second year of treatment. The presence of valvular heart disease, defined as aortic regurgitation of mild or greater severity and/or mitral regurgitation of moderate or greater severity, was assessed using two-dimensional, color Doppler and pulsed- and continuous-wave Doppler examinations. RESULTS: At 2 years, the 21 patients had a mean reduction in initial weight of 13.9 + 10.0%, which was significantly (p<0.001) smaller than their 1-year loss of 17.1 +/- 8.7%. Nine of 21 patients reported that they took fen-phen irregularly during the last 4 months of the study because of fears of developing health complications. These nine patients had a 2-year weight loss of 8.7 +/- 7.5%, compared with a significantly (p<0.04) larger loss of 17.6 +/- 10.5% for participants who reported taking medication regularly. Six of 20 (30%) patients met criteria for valvular heart disease. None of the six had signs or symptoms of this condition. DISCUSSION: Fenfluramine was withdrawn from the market on September 15, 1997 because of concerns that it was associated with valvular heart disease. The present findings are discussed in terms of the potentially favorable long-term benefits of combining lifestyle modification with weight loss medications that are both safe and effective.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9688104&dopt=Abstract
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infonet.tufts.edu
The activity of D-fenfluramine, L-fenfluramine, and phentermine as inhibitors of five human cytochromes P450 was evaluated using human liver microsomes in vitro. All three compounds produced negligible inhibition of P450-1A2, -2C9, -2E1, and -3A. Phentermine also did not inhibit P450-2D6. However, D- and L-fenfluramine significantly inhibited P450-2D6 activity as measured by dextromethorphan O-demethylation, with mean 50% inhibitory concentrations (15.1 microM) within one order of magnitude of that for fluoxetine (2.7 microM). Findings from the in vitro assay are consistent with clinical studies showing significant inhibition of desipramine clearance by coadministration of fenfluramine.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9690701&dopt=Abstract
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Synapse. 1998 Sep;30(1):107-11.
Evaluation of the conditioned reinforcing effects of phentermine and fenfluramine in the rat: concordance with clinical studies.
Rea WP, Rothman RB, Shippenberg TS.
Integrative Neuroscience Unit, Behavioral Neuroscience Laboratory, Division of Intramural Research, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.
An unbiased place-preference conditioning procedure was used to characterize the conditioned reinforcing effects of phentermine (PHEN), fenfluramine (FEN), and their combination (PHEN/FEN) in previously drug-naive rats. Animals exhibited marked preferences for an environment previously associated with the administration of phentermine. The minimum dose producing a significant effect was 3.0 mg/kg. In contrast, FEN produced dose-related place aversions. In animals which received a subthreshold dose of FEN in combination with a dose of PHEN that produced a conditioned place preference, no preference or aversion for the drug-paired place was seen. Similarly, no significant conditioning in response to administration of PHEN (3.0 mg/kg) and FEN (3.0 mg/kg) was seen. The failure of PHEN/FEN to produce conditioned reinforcing effects is in line with recent clinical studies, and suggests that PHEN/FEN and drug combinations sharing the same neurochemical mechanisms of action will have low potential for abuse.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9704887&dopt=Abstract
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