(+)-Amphetamine, (+/-)-ephedrine, and phentermine are commonly used appetite suppressants that release monoamines from nerve cells by acting as substrates for biogenic amine transporters. One key difference among the three drugs is their selectivity for norepinephrine (NE) release vs. dopamine (DA) release. The NE/DA selectivity ratios for these drugs as determined in vitro [(EC50 NE(-1))/(EC50 DA(-1))] are (+/-)-ephedrine (18.6) > phentermine (6.7) > (+)-amphetamine (3.5). The in vitro data suggest that when administered in vivo, these stimulants might differ in their ability to release DA from nerve terminals in the brain. To test this hypothesis, noradrenergic effects (i.e., plasma NE) and dopaminergic effects (i.e., central DA release) were assessed when each drug was administered intravenously (1.5 mg/kg) to anesthetized baboons. Central DA release was determined via positron emission tomography using the method of [11C]raclopride displacement. In the present investigation, high doses of these stimulants increased plasma NE and DA in parallel, but only (+)-amphetamine released central DA from neurons and decreased plasma prolactin. None of the drugs altered plasma amine metabolite levels, indicating no inhibition of monoamine oxidase activity at the administered doses. Plasma drug levels measured in baboons were higher than those measured in human patients taking prescribed doses of the drugs. Viewed collectively, the present data indicate that typical clinical doses of phentermine and (+/-)-ephedrine may not release central DA in humans, a hypothesis that should ultimately be tested in controlled clinical studies.
"In addition, this medication increases the effects of serotonin (5-hydroxytryptamine, 5-HT) by suppressing monoamine oxidase and preventing 5-HT from being removed by the lungs. Compared to amphetamine, which has a similar chemical structure to phentermine, phentermine does not affect the secretion and resorption of dopamine, so it has been reported that phentermine has a very low chance of substance abuse or misuse.5-8) "
[Show abstract][Hide abstract] ABSTRACT: Obesity is a complex problem that is now considered a chronic metabolic disease. In Korea, phentermine has been widely used for the treatment of obesity in the primary care setting since 2004. However, there have been very few studies on the safety and efficacy of phentermine. To investigate the safety and efficacy of this drug, a postmarketing surveillance study was performed.
A total of 795 patients with obesity (body mass index ≥ 25 kg/m(2)) were enrolled from 30 primary care centers in Korea from September 2006 to November 2007. Patients were examined to ascertain safety and efficacy at 4-, 8-, and 12-week intervals. The criterion for efficacy was defined as a weight loss ≥ 5% of body weight.
Of the 795 enrolled patients, 735 (92.5%) were evaluated in safety assessments and 711 (89.4%) was included in efficacy assessments. A total of 266 adverse events (AEs) were reported by 218 patients (30.6%), and no serious AEs were reported. Among 711 patients, 324 patients (45.6%) lost ≥ 5% of their body weight. The mean weight loss was 3.8 ± 4.0 kg.
AEs are commonly associated with phentermine, even though phentermine is effective for weight loss and relatively well-tolerated.
Korean Journal of Family Medicine 09/2013; 34(5):298-306. DOI:10.4082/kjfm.2013.34.5.298
"The answer to this discrepancy may lie in the inability of phentermine to act in the central nervous system (CNS). Alexander et al.25) compared the amount of central DA release in baboons via positron emission tomography after injecting them with amphetamine, phentermine and ephedrine, and reported that only amphetamine was able to release DA from CNS neurons and decrease plasma prolactin. Thus, this result may suggest that the low or absent addiction potential of phentermine is, in part, due to its low activity in the CNS. "
[Show abstract][Hide abstract] ABSTRACT: A safe and effective way to control weight in patients with affective disorders is needed, and phentermine is a possible candidate. We performed a PubMed search of articles pertaining to phentermine, sibutramine, and affective disorders. We compared the studies of phentermine with those of sibutramine. The search yielded a small number of reports. Reports concerning phentermine and affective disorders reported that i) its potency in the central nervous system may be comparatively low, and ii) it may induce depression in some patients. We were unable to find more studies on the subject; thus, it is unclear presently whether phentermine use is safe in affective disorder patients. Reports regarding the association of sibutramine and affective disorders were slightly more abundant. A recent study that suggested that sibutramine may have deleterious effects in patients with a psychiatric history may provide a clue for future phentermine research. Three explanations are possible concerning the association between phentermine and affective disorders: i) phentermine, like sibutramine, may have a depression-inducing effect that affects a specific subgroup of patients, ii) phentermine may have a dose-dependent depression-inducing effect, or iii) phentermine may simply not be associated with depression. Large-scale studies with affective disorder patients focusing on these questions are needed to clarify this matter before investigation of its efficacy may be carried out and it can be used in patients with affective disorders.
Clinical Psychopharmacology and Neuroscience 04/2013; 11(1):7-12. DOI:10.9758/cpn.2013.11.1.7
"Besides, we expanded our findings that the inhibition of NPY was related to the release of endogenous catecholamine in the brain as pre-treatment with AMPT could abolish this inhibition. Therefore, NPY might be essential for the appetite-suppressing effect of AMPH-like anorectic drugs as it participated in the anorectic effect of AMPH (Hsieh et al. 2006), methAMPH (Crowley et al. 2005) and ephedrine (Kim et al. 2004), which released monoamine as a mediator (Alexander et al. 2005). "
[Show abstract][Hide abstract] ABSTRACT: Hypothalamic neuropeptide Y (NPY) has been reported to involve in regulating behavioral response of phenylpropanolamine (PPA), a sympathomimetic agent. This study explored if protein kinase C (PKC)-delta signaling participated in this regulation. Moreover, possible roles of anti-free radical enzyme catalase (CAT) and nitrogen oxide synthase (NOS) were also examined. Rats were treated daily with PPA for 4 days. Changes in food intake and hypothalamic NPY, PKCdelta, CAT, and NOS contents were assessed and compared. Results showed that PKCdelta and CAT increased during PPA treatment, which were concomitant with decreases in NPY content and food intake, while the change of NOS was expressed differently. Moreover, PKCdelta knockdown could modify PPA anorexia as well as NPY and CAT expression, while NOS expression remained unchanged. Furthermore, pre-treatment with NOS inhibitor could modify both PPA anorexia and NPY content. It is suggested that PKCdelta participates in the anorectic response of PPA via the modulation of NPY and CAT, while NOS contribute to this modulation via a different mechanism during PPA treatment. Results provide molecular mechanism of NPY-mediated PPA anorexia and may aid the therapeutic research of PPA and other anti-obesity drugs.
Journal of Neurochemistry 08/2010; 114(4):1217-30. DOI:10.1111/j.1471-4159.2010.06843.x · 4.28 Impact Factor
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