The effect of propranolol phentolamine and pimozide on drug-induced anorexia in the mouse. Effects on serotonin in rat hypothalamus of D-fenfluramine, aminorex, phentermine and fluoxetine. Appetite suppressants and valvular heart disease in a population-based sample: the HyperGEN study. Ionamin online references

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Psychopharmacology (Berl). 1979;66(3):297-300.
The effect of propranolol phentolamine and pimozide on drug-induced anorexia in the mouse.

Dobrzanski S, Doggett NS.

Pimozide was a potent antagonist of (+)amphetamine, diethylpropion, mazindol and phentermine anorexia in the mouse. Phentolamine and propranolol produced no such antagonism, but either potentiated or had no effect on the drug-induced anorexia. Although the mechanism of action of the four anorectic agents appears to involve dopamine receptor agonist activity, an antagonist or partial agonist effect at noradrenergic receptors may also be involved.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=119276&dopt=Abstract

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Eur J Pharmacol. 2002 Jun 7;445(1-2):69-81.
Effects on serotonin in rat hypothalamus of D-fenfluramine, aminorex, phentermine and fluoxetine.

Tao R, Fray A, Aspley S, Brammer R, Heal D, Auerbach S.

Nelson Laboratories, Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, NJ 08854-8082, USA.

Hypothalamic 5-HT (serotonin) regulates food intake, energy expenditure and bodyweight. Using in vivo microdialysis, we determined the effects of various anorectic drugs on hypothalamic extracellular 5-HT levels during the dark phase when rats predominantly feed. Phentermine and aminorex, which were originally considered to be catecholaminergic drugs, markedly increased 5-HT efflux in rat hypothalamus. Their actions were less profound than D-fenfluramine, but considerably greater than that of the selective 5-HT reuptake inhibitor, fluoxetine. This suggests that enhanced hypothalamic 5-HT function could be involved in their anorectic actions. Pharmacological characterization revealed that D-fenfluramine, aminorex and probably also phentermine potentiate synaptic 5-HT function predominantly by release, whereas fluoxetine acts exclusively by reuptake inhibition. The results also revealed that the combined actions of phentermine and D-fenfluramine on hypothalamic extracellular 5-HT levels were additive, but not synergistic. In contrast, there was a significant negative cooperative effect on extraneuronal 5-HT of combining phentermine with fluoxetine.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12065196&dopt=Abstract

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Am J Med. 2002 Jun 15;112(9):710-5.
Appetite suppressants and valvular heart disease in a population-based sample: the HyperGEN study.

Palmieri V, Arnett DK, Roman MJ, Liu JE, Bella JN, Oberman A, Kitzman DW, Hopkins PN, Morgan D, de Simone G, Devereux RB.

Weill Medical College of Cornell University, New York, New York 10021, USA.

PURPOSE: Previous studies of the association between the use of appetite suppressants and valvular heart disease have not accounted for the effects of valvular structure and aortic root diameter, which are associated with obesity. We assessed whether the use of the appetite suppressants fenfluramine/dexfenfluramine, either alone or with phentermine, was associated with aortic regurgitation while adjusting for these variables. SUBJECTS AND METHODS: The sample included 2524 adult participants in the population-based Hypertension Genetic Epidemiology Network study. Information regarding current drug use was assessed during a clinical examination. Medication use was continued at the time of echocardiographic study. 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. RESULTS: Nineteen participants, all of whom had hypertension, were being treated with fenfluramine or dexfenfluramine (5 on these agents alone, 14 also with phentermine). Aortic regurgitation was present in 32% (n = 6) of those taking fenfluramine or dexfenfluramine versus 6% (162/2505) of remaining subjects (P = 0.001). In multivariate-adjusted analyses, treatment with fenfluramine or dexfenfluramine was associated with aortic regurgitation (odds ratio [OR] = 4.9; 95% confidence interval [CI]: 1.7 to 14) and aortic fibrocalcification (OR = 5.2; 95% CI: 1.9 to 15). 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.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12079711&dopt=Abstract

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