Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new phentermine research articles will be listed here shortly after becoming available to us.
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Medical research on phentermine
Int J Obes (Lond). 2008 Jun 17;
Roth JD, Trevaskis JL, Wilson J, Lei C, Athanacio J, Mack C, Kesty NC, Coffey T, Weyer C, Parkes DG
Objective:To characterize the interactive effects of amylin with phentermine or sibutramine on food intake, body weight/composition and gene expression in diet-induced obese (DIO) rats.Design:DIO rats were intraperitoneally injected with a single dose of amylin (10 mug kg(-1)) and/or phentermine (1 mg kg(-1)) or chronically infused with amylin (100 mug kg(-1) d(-1)) or vehicle with or without phentermine (0.5-10 mg kg(-1) d(-1)) or sibutramine (3 mg kg(-1) d(-1)) using two surgically implanted subcutaneous osmotic mini-pumps.Measurements:Twenty-four hour food intake, locomotor activity and components of meal microstructure (meal size, latency, duration and intermeal interval) were measured following acute administration (amylin, phentermine or amylin+phentermine). Body weight and composition (for amylin and/or sibutramine or phentermine) and metabolism-related gene mRNA expression in the liver (fatty acid synthase, stearoyl-CoA desaturase-1 and carnitine palmitoyltransferase-1) and brown fat (beta-adrenergic receptors and uncoupling protein-1) were measured (for amylin and/or phentermine) after sustained infusion (2 weeks).Results:Acute co-administration of amylin (10 mug kg(-1)) and phentermine (1 mg kg(-1)) reduced acute food intake (up to 19 h) more than either monotherapy. In two studies, sustained subcutaneous infusion of amylin for 2 weeks decreased cumulative food intake (22%) and vehicle-corrected body weight gain ( approximately 4-8%). Phentermine's anorexigenic (10-17%) and weight-reducing effects ( approximately 0-5%) were only evident at the highest dose tested (10 mg kg(-1) d(-1)). Combination of amylin (100 mug kg(-1) d(-1)) and phentermine reduced food intake (30-43%), body weight (8-12%) and adiposity to a greater extent than either monotherapy. Amylin prevented phentermine-induced reductions in UCP-1 mRNA in brown adipose tissue. When amylin+sibutramine were infused, mathematically additive decreases in food intake (up to 45%) and body weight (up to 12%) were evident. Similar to amylin+phentermine treatment, amylin+sibutramine mediated weight loss was attributable to significant reductions in fat mass.Conclusions:Combined treatment of DIO rats with the pancreatic beta-cell hormone amylin and phentermine or sibutramine resulted in additive anorexigenic, weight- and fat-reducing effects.International Journal of Obesity advance online publication, 17 June 2008; doi:10.1038/ijo.2008.91.
Toxicol Pathol. 2008; 36(2): 204-17
Donnelly KB
Recent voluntary withdrawal of the ergoline-derivative Alzheimers' drug Pergolide (Permax) resulting from demonstrated risk of cardiac valve injury illustrates the increased importance of valve injury in pharmaceutical toxicology. Following the 2001 landmark discovery of cardiac valve injury associated with the widely prescribed anti-obesity drug combination fenfluramine-phentermine, and subsequent withdrawal, the need to understand and assess cardiac valve biology and pathology both preclinically and clinically has been accentuated. Unique aspects of the developmental biology, anatomy, and physiology of cardiac valves compared to main cardiac tissue have been discovered, and key elements of the pathophysiology of various valvular injury mechanisms have been described. Although general clinical cardiac valvular disease in humans has been well characterized, animal modeling of valvular injury has proved to be difficult and undersubscribed. Additionally, both the preclinical, pharmaceutical, toxicologic assessment of valvular injury and the understanding of species-comparative valvular pathology have been limited. As discoveries and awareness grows, the purpose of this paper is to review the structure and function of cardiac valves, mechanisms, and outcomes of the common acquired human cardiac valve diseases, including those that are drug-related; to summarize comparative laboratory animal valvular pathology; and to review the literature of contemporary animal models of valvular injury.
Pharmacol Biochem Behav. 2008 Sep; 90(3): 339-43
Wellman PJ
In the 1990s, phentermine was combined with either fenfluramine or its active enantiomer dexfenfluramine to promote weight loss. Appetite suppressants are known to alter pain reactivity. The current experiment examined the acute impact of phentermine (0, 2.5, 5, 10, or 20 mg/kg) on paw-lick/jump latencies recorded just before and at 10, 20, and 30 min after phentermine injection. In addition, separate groups of rats were treated with 1, 2, or 4 mg/kg dexfenfluramine or with selected combinations of phentermine with dexfenfluramine. Phentermine induced significant analgesia in rats at a dose of 2.5 mg/kg, whereas only the 4.0 mg/kg dose of dexfenfluramine induced significant analgesia. Combinations of 1 mg/kg dexfenfluramine or 2 mg/kg dexfenfluramine with phentermine were mostly additive in terms of changes in analgesia scores. The present results characterize the analgesic action of phentermine, further confirm the analgesic action of dexfenfluramine and suggest an additive analgesic effect for the combination of dexfenfluramine with phentermine.
Clinical experience of a carbohydrate-restricted diet for the metabolic syndrome.
Metab Syndr Relat Disord. 2004; 2(3): 180-6
Vernon MC, Kueser B, Transue M, Yates HE, Yancy WS, Westman EC
Background: Our objective was to analyze a restricted carbohydrate dietary approach compared to a standard low-fat diet plus medication plan as treatment for weight loss and the metabolic syndrome. Methods: This was a retrospective analysis of patients attending an outpatient weight and metabolism management program, including periodic individual visits combined with either a carbohydrate-restricted diet (with multivitamin and essential fatty acids supplementation) or low-fat/low-calorie diet + phentermine/fenfluramine. The main outcome measurements were total body weight and fasting serum lipid profiles. Clinical data were maintained on standardized flow sheets. Results: One hundred twenty-two patients had complete baseline and follow-up information. Sixty-six were treated with a carbohydrate-restricted diet without medication, and 56 were treated with a combination of low-fat/low-calorie diet and medication. Weight loss occurred in both groups, but was greater in the medication group: the carbohydrate-restricted group lost a mean of 9.5 kg over 15.0 weeks (0.63 kg/week); the low-fat/low-calorie diet + medication group lost a mean of 14.1 kg over a mean duration of 20.2 weeks (0.70 kg/week), p < 0.01. The carbohydrate-restricted group had a greater reduction in triglycerides (p = 0.02) and triglyceride/HDL ratio (p = 0.01), and a greater increase in HDL (p < 0.001) than the medication group. Conclusions: In this outpatient program, a carbohydrate-restricted diet and a low-fat/low-calorie diet + medication led to weight loss, but the carbohydrate-restricted diet had a more favorable effect on triglycerides and HDL. Because of the effects on weight, triglycerides, and HDL, a carbohydrate-restricted diet may be useful for the treatment of metabolic syndrome.
Abuse liability assessment of atomoxetine in a drug-abusing population.
Drug Alcohol Depend. 2008 May 1; 95(1-2): 140-6
Jasinski DR, Faries DE, Moore RJ, Schuh LM, Allen AJ
BACKGROUND: Atomoxetine is a non-amphetamine medication approved to treat ADHD in children, adolescents, and adults. Previous studies demonstrated low abuse potential for atomoxetine in recreational drug users. This study assessed the abuse potential of atomoxetine in stimulant-preferring drug abusers compared to methylphenidate and phentermine as positive controls and desipramine and placebo as negative controls. METHODS: Forty male and female, 32-53 years old stimulant-preferring drug abusers completed this balanced Latin-square designed study. Subjects received acute, double-blind doses of placebo, desipramine (100 and 200 mg), methylphenidate (90 mg), phentermine (60 mg), and atomoxetine (45, 90, and 180 mg). Subjective and physiological effects were collected for 24 h following each drug treatment. RESULTS: Methylphenidate and phentermine were liked significantly more than placebo, atomoxetine, or desipramine. No atomoxetine dose was liked significantly more than placebo and liking scores for atomoxetine were similar to, or significantly lower than, desipramine, as assessed by the Drug Rating Questionnaire-Subject. While atomoxetine 45 and 180 mg did not significantly change any Addiction Research Center Inventory (ARCI) scores, atomoxetine 90 mg significantly increased A and BG stimulant scores of the ARCI and both methylphenidate and phentermine produced greater A and BG increases than any atomoxetine dose and also increased MBG (euphoria) scores relative to placebo. CONCLUSIONS: Atomoxetine has significantly less abuse liability than methylphenidate or phentermine and no greater abuse liability than desipramine.
Longitudinal effects of fenfluramine-phentermine use.
Angiology. 2007 Dec-2008 Jan; 58(6): 772-3; author reply 774
Bhattacharyya S, Constantin C, Davar J, Mikhailidis D
Myocardial infarction induced by appetite suppressants in Malaysia.
N Engl J Med. 2007 Nov 1; 357(18): 1873-4
Azarisman SM, Magdi YA, Noorfaizan S, Oteh M
Eur J Anaesthesiol. 2008 Apr; 25(4): 299-306
Murali Krishna T, Panda NB, Batra YK, Rajeev S
BACKGROUND: Intrathecal ketamine produces a short period of analgesia with stable haemodynamics. Midazolam with bupivacaine prolongs the duration of analgesia when administered intrathecally but does not prevent hypotension. The objective of this study was to assess the effect of a combination of intrathecal bupivacaine, ketamine and midazolam on the duration of analgesia and haemodynamic parameters. METHODS: A prospective, randomized, double-blind study was carried out in 60 ASA I and II patients undergoing lower limb surgery under spinal anaesthesia. Patients were divided into three groups of 20 each. Patients in all the three groups received 3 mL of hyperbaric bupivacaine (0.5%) intrathecally. In addition, patients in Groups II and III received intrathecal ketamine (0.1 mg kg-1) and the same dose of ketamine along with midazolam (0.02 mg kg-1), respectively. All patients were evaluated for block characteristics, duration of pain-free period, total rescue analgesic requirement in the 24-h postoperative period, total dose of mephenteramine to treat hypotension and any central or neurological complication. RESULTS: No patients in Group II required mephenteramine while 40% of patients in Group I and 10% in Group III required mephenteramine to maintain blood pressure after spinal anaesthesia. The mean +/- standard deviation duration of pain-free period was 331.5 +/- 89.9, 369.7 +/- 124.2 and 730.5 +/- 81.5 min in Group I, II and III, respectively. The pain-free interval was significantly greater in Group III compared to Groups I and II (P < 0.001). No patient had any complications. CONCLUSION: A low dose of midazolam and ketamine with bupivacaine intrathecally results in prolonged analgesia and less haemodynamic fluctuations. However, the safety of this combination needs to be proved before its use in clinical practice.
The longitudinal effects of fenfluramine-phentermine use.
Angiology. 2007 Jun-Jul; 58(3): 353-9
Fleming RM, Boyd LB
The use of previous anorectic medications and the combined use of the anorectic medications fenfluramine and phentermine (Fen-Phen) have been associated with varying degrees of valvular regurgitation and pulmonary hypertension. More recent reports have suggested a lower incidence of both than was previously reported. Comparisons of patients with similar body mass index (BMI) have been missing as well as information regarding chamber dimensions and pressures. Using transthoracic 2D, M-mode, and Doppler echocardiography, 57 men and women (30 Fen-Phen and 27 BMI-matched individuals/BMIMCG) were studied to determine their chamber dimensions, wall motion, diastolic function, valvular abnormalities, left ventricular ejection fractions (LVEFs), and pulmonary artery pressures (pAPs). The 30 Fen-Phen subjects were studied shortly after discontinuing the medications and again 6 to 12 months later. The results in these subjects were then compared with the valvular findings of 660 randomly selected cardiac patients with non-Fen-Phen-induced heart disease (NFPHD). Valvular regurgitation was greatest among patients who had recently discontinued the use of Fen-Phen (EFP) with 57% of all valves having regurgitation, 87.5% of which were "mild." These same individuals also had the largest left ventricles at end (LVEDD) diastole (5.03 +/-0.22 cm) and systole (LVESD). The LVESDs were statistically larger (p
J Anal Toxicol. 2007 May; 31(4): 208-13
Apollonio LG, Whittall IR, Pianca DJ, Kyd JM, Maher WA
The aim of this study was to evaluate the Bio-Quant Direct ELISA assays for amphetamine and methamphetamine in the routine presumptive screening of biological fluids. Standard concentration curves of the target analytes were assayed to assess sensitivity, and known concentrations of common amphetamine-type substances (ephedrine, pseudoephedrine, phentermine), designer analogues (MDA, MDMA, MDEA, MBDB, PMA, 4-MTA, 2CB), and putrefactive amines (phenylethylamine, putrescine, tryptamine, tyramine) were analyzed to determine cross-reactivity. Results of the standard curve studies show the capacity of both Direct ELISA kits to confidently detect down to 3 ng/mL interday (PBS matrix; CVs 6.3-15.5%). Cross-reactivity relative to that of 50 ng/mL preparations of the target compounds demonstrated that the Direct ELISA kit for amphetamine also detected MDA (282%), PMA (265%), 4-MTA (280%), and phentermine (61%), and the Direct ELISA for methamphetamine also assayed positive for MDMA (73%), MDEA (18%), pseudoephedrine (19%), MBDB (8%), and ephedrine (9%). Matrix studies demonstrated that both ELISA kits could be applied to screening of blood, urine, and saliva to a concentration of 6 ng/mL or lower. In conclusion, the Bio-Quant Direct ELISA kits for amphetamine and methamphetamine are fast and accurate and have demonstrated themselves to be useful tools in routine toxicological testing.