Ionamin online research references
Synapse. 2000 May;36(2):102-13.
Effects of phentermine and fenfluramine on extracellular dopamine and serotonin in rat nucleus accumbens: therapeutic implications.
Baumann MH, Ayestas MA, Dersch CM, Brockington A, Rice KC, Rothman RB.
Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.
Combined administration of the amphetamine analogs phentermine and fenfluramine (PHEN/FEN) has been used in the treatment of obesity. While these medications are thought to modulate monoamine transmission, the precise neurochemical effects of the PHEN/FEN mixture have not been extensively studied. To assess the mechanism of PHEN/FEN action, in vivo microdialysis studies were performed in the nucleus accumbens of conscious freely moving rats. A series of amphetamine derivatives including phentermine, chlorphentermine, fenfluramine, and PHEN/FEN (1:1 ratio), were infused locally into the accumbens via reverse-dialysis (1, 10, 100 microM) or injected systemically (1 mg/kg, ip). Dialysate samples were assayed for dopamine (DA) and serotonin (5-HT) by high-performance liquid chromatography with electrochemical detection. When infused locally, phentermine preferentially increased extracellular DA, whereas fenfluramine selectively increased extracellular 5-HT. Local administration of chlorphentermine or the PHEN/FEN mixture caused parallel elevations of both transmitters. Analogous results were obtained when the drugs were injected systemically. Phentermine stimulated robust locomotor activity in mice, whereas chlorphentermine and fenfluramine did not. PHEN/FEN caused modest locomotor stimulation after a low dose, but had no effect at the highest dose. Accumulating evidence suggests that chronic drug and alcohol abuse is associated with deficits in both DA and 5-HT neuronal function. Thus, dual activation of DA and 5-HT neurotransmission with monoamine releasing agents may be an effective treatment strategy for substance use disorders, as well as for obesity. Synapse 36:102-113, 2000. Published 2000 Wiley-Liss, Inc.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10767057&dopt=Abstract
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J Heart Valve Dis. 2000 Mar;9(2):256-60; discussion 260-1.
Expression of 5-hydroxytryptamine receptor subtype messenger RNA in interstitial cells from human heart valves.
Roy A, Brand NJ, Yacoub MH.
Department of Cardiothoracic Surgery, Imperial College School of Medicine, National Heart and Lung Institute, Heart Science Centre, Harefield Hospital, Middlesex, UK.
BACKGROUND AND AIM OF THE STUDY: Severe heart valve disorder has been reported in patients receiving a combination of the anorectic drugs fenfluramine and phentermine. The exact molecular mechanisms involved remain unknown. Fenfluramine alters the serotonin level in the brain, while phentermine interferes with the pulmonary clearance of serotonin; these data suggest that serotonin levels affect regulation of valve function. The aim of the present study was to characterize the serotonin receptor (5-hydroxytryptamine) subtypes expressed in the interstitial cells of human heart valves. METHODS: Interstitial cells were isolated and cultured from the aortic, pulmonary, mitral and tricuspid valves of recipient hearts obtained during transplantation. Total RNA was extracted from cultured cells in order to determine gene expression by reverse transcription-polymerase chain reaction (RT-PCR) using 5-hydroxytryptamine (5-HT) subtype-specific primer pairs. RESULTS: The results show that: (i) 5-HT 1B and 1D receptor subtypes are expressed in all four heart valves. This is significant as the 1B and 1D receptor subfamilies are the target of the anti-migraine drug sumatriptan, and these receptors regulate cardiac function and movement; (ii) 5-HT 1A, 5-HT 1E and 5-HT 1F are not expressed in interstitial cells isolated from the valves. CONCLUSION: We conclude that preliminary evidence exists for the presence of distinct subsets of 5-HT receptors in human heart valves, indicating that interstitial cells of the valves potentially respond to serotonin levels.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10772044&dopt=Abstract
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Behav Pharmacol. 1999 Dec;10(8):775-84.
Effects of phentermine on responding maintained by progressive-ratio schedules of cocaine and food delivery in rhesus monkeys.
Stafford D, LeSage MG, Glowa JR.
Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport 71130-3932, USA.
Previous reports indicate that intravenous pretreatment with phentermine can decrease cocaine-maintained responding without affecting food-reinforced responding under fixed-ratio schedules. The present experiments were designed to explore the generality of this effect using progressive-ratio schedules of reinforcement and different routes of phentermine administration. Unit doses of cocaine and food-pellet magnitudes were identified that maintained similar breaking points, and the effects of acute exposure to phentermine were assessed. In Experiment 1, a 'conventional' (one-trial) progressive-ratio schedule was used, in which response requirements increased after each reinforcer delivery; in Experiment 2, a 'modified' (five-trial) progressive-ratio schedule was used, in which response requirements increased after every five reinforcer deliveries. In one group of monkeys, responding was maintained by food; in another, cocaine infusions maintained responding. Phentermine (0.1-5.6mg/kg, intramuscularly (i.m.)) dose-dependently decreased breakpoints on both progressive-ratio schedules. There were no differences in phentermine's effects on cocaine- and food-maintained behavior. In Experiment 3, intravenous administration of phentermine had largely similar effects. Taken together with results from previous reports, these data suggest that the effects of phentermine pretreatment are influenced by the behavioral procedure used to maintain responding and/or by the efficacy of the food and cocaine reinforcers.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10780293&dopt=Abstract
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