• YAKHAK HOEJI
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• v.42 no.6
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• pp.576-582
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• 1998

Fenfluramine, an anorectic agent, is widely abused as a diet pill in Korea because it is freely marketed in China without any regulation. The optical isomers of fenfluramine hav e different phamacological actions: d-form is used as an anorectic agent, while l-form as a neuroleptic agent. To investigate the metabolism when racemic fenfluramine was administered orally, the urinary excretion of fenfluramine was studied in rats. The enantiomeric separation of fenfluramine was performed on achiral column by gas chromatography using (S)-N-(trifluoroacetyl)-l-prolyl chloride (TFP) as a derivatizing agent. After administration of 15mg/kg of racemic fenfluramine to rats, d-, l-fenfluramine and its metabolites d- and l norfenfluramine in urine were determined by chromatographic separation of TFP derivatives on DB-1 at retention time of 11.2, 11.8, 8.4 and 8.6 min respectively. Urinary recoveries of d and l-fenfluramine in rat were 0.42-5.9O% and 0.18-1.20% respectively in urine specimens collected during first 24hr. The comparison in the levels of isomers showed that d- fenfluramine were higher than l-form, while d-norfenfluramine were lower than l-form. The ratios between parent compound and metabolite revealed that d-norfenfluramine to d-fenfluramine ranged from 1.0 to 4.4, while the ratio of l-norfenfluramine to l-fenfluramine was 8.2-21.1 indicating that l-fenfluramine is metabolized faster than the d-isomer.

• YAKHAK HOEJI
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• v.47 no.5
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• pp.266-270
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• 2003

We evaluated four commercially available methamphetamine immunoassays for their relative cross-reactivities of amphetamine analogues in human urine: Abbott TDx, Vitalab Selectra and on-site test kits (Accusign MET, SD bioline MET). High cross-reactivities were shown at designer's drugs such as methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA) and methylenedioxyethylamphetamine (MDEA) in all of the tested immunoassays. Methoxyphenamine, fenfluramine and phentermine were positive in TDx and Selectra, but were not positive in on-site test kits. Pseudoephedrine, norpseudoephedrine, ephedrine, norephedrine, MDMA, MDA, fenfluramine and phentermine were detected by gas chromatography/mass spectrometry(GC/MS) in false positive urines. Since the overall specificity of any of the devices was not 100％, we found it is important to confirm any positive screening test result, so we developed simultaneous determination of amphetamine analogues in urines. After alkalinization of the urine samples with 6-N NaOH, the analytes were extracted using ethyl acetate, derivatized with pentafluoropropyl anhydride (PFPA) prior at GC/MS analysis.

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.126.2-127
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• 2000

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.4 no.1
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• pp.27-38
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• 1993

Pervasive developmental disorder is one of the most severe clinical disorder in child psychiatry and is associated with deviancies in multiple areas of development. Medication does not cure pervasive developmental disorder and its effectiveness is generally nonspecific. But psychopharmacological treatment can be important for some children with pervasive developmental disorder and can make many young autistics more amenable to behavior modification and education. Haloperidol, the most widely studied antipsychotics, was statistically and clinically superior to placebo, and furthermore, was known to facilitate the positive functioning such as, discrimination learning and imitative communication, without side effects. However, administration of haloperidol is associated with drug related dyskinesia, and it warrants the introduction and use of the other novel drugs. Several biochemical studies suggest that subgroups of children with pervasive developmental disorder show hyperserotonemia and increased endogenous opioid level as compared with controls. Psychopharmacological trials were conducted according to these findings(ex : fenfluramine, naltrexone), with mixed results till now. These and another drugs that have been used in children with pervasive developmental disorder and their effectiveness are reviewed.

• Korean Journal of Biological Psychiatry
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• v.4 no.2
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• pp.179-187
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• 1997

The clinical efficacy of serotonin reuptake inhibitors such as clomipramine in the treatment of obsessive compulsive disorder(OCD) has fueled interest in the neurobiological basis of this illness. OCD is responsive exclucively to potent serotonin reuptake inhibitors clomipramine, fluoxetine, fluvoxamine, sertraline, and paroxetine and this point forms the important evidence supporting a cental role for serotonin in the pathogenesis of the disorder. Other serotonergic medications such as lithium, buspirone, trazodone, or fenfluramine may be useful as adjuvant treatments in treatmentrefractory OCD and adjuvant antipsychotics are useful in tic disorders, personality disorders, and psychotic disorders. This paper reviews results of treatment studies, investigations of biological markers, and neuroendocrine challenges and implications for the role of serotonin in pathophysiology and treatment of OCD.

• Korean Journal of Biological Psychiatry
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• v.4 no.2
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• pp.188-193
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• 1997

Along with psychosocial factors of suicide, biological backgrounds of suicide are explored by extensive works mostly on biological markers, neurobiological models, genetic bases, and relationships with aggression and violence. The biology of suicide confers on neurotransmitters in central nervous system exploring metabolites, receptor binding affinities, neuroendocrine challenge tests in brain, cerebrospinal fluid, blood and etc. The major concerns with suicide are focused mainly on serotonin system : low CSF 5-HIAA concentration, higher $5-HT_2$ receptor binding, and blunt prolactin response to fenfluramine. Postmortem study, in vivo study, genetic contributions, and some other issues such as suicidal methods, serum cholesterol, alcohol, and selective serotonin reuptake inhibitors are reviewed and discussed.

• Korean Journal of Psychosomatic Medicine
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• v.3 no.2
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• pp.197-206
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• 1995

Obesity is a major nutritional problem in the developed countries. The prevalence of obesity may range from 10 to 50 per rent or mort of adult population and it may be increasing tendency. Many efforts have been made to understand the pathogenesis of obesity, but except a few metabolic obesities in the most of obese patients, the mechanisms are not understood. The treatment modalities of obesity, ranging from dietary and pubilc health intervention through the pharmacological and surgical therapy, have been developed and tested. In the obese patients mortalities and mobilities are significantly increased than non obese subjects due to hypertension, diabetics, and other problems. There are four possible mechanisms by which energy balance might be altered to enhance metabolic efficiency. futile metabolic pathway, alteration of protein rum over, alteration in sodium-potassium ATPase and alteration in uncoupled oxidation in brown adipose tissue are considered as possible mechanisms. Low calory and very low calory diets are recommended as a dietary program. Several pharmacological agent such as benzphetamine, fenfluramine, mazindol and fluoxetin are currently popular drugs for the treatment of obesity.

• Biomolecules & Therapeutics
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• v.20 no.6
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• pp.506-512
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• 2012

Although pruritus is the critical symptom of atopic dermatitis that profoundly affect the patients' quality of life, controlling and management of prurirtus still remains as unmet needs mainly due to the distinctive multifactorial pathogenesis of pruritus in atopic dermatitis. Based on the distinct feature of atopic dermatitis that psychological state of patients substantially influence on the intensity of pruritus, various psychotropic drugs have been used in clinic to relieve pruritus of atopic dermatitis patients. Only several psychotropic drugs were reported to show real antipruritic effects in atopic dermatitis patients including naltrexone, doxepin, trimipramine, bupropion, tandospirone, paroxetine and fluvoxamine. However, the precise mechanisms of antipruritic effect of these psychotropic drugs are still unclear. In human skin, serotonin receptors and serotonin transporter protein are expressed on skin cells such as keratinocytes, melanocytes, dermal fibroblasts, mast cells, T cells, natural killer cells, langerhans cells, and sensory nerve endings. It is noteworthy that serotonergic drugs, as well as serotonin itself, showed immune-modulating effect. Fenfluramine, fluoxetine and 2, 5-dimethoxy-4-iodoamphetamine significantly decreased lymphocyte proliferation. It is still questionable whether these serotonergic drugs exert the immunosuppressive effects via serotonin receptor or serotonin transporter. All these clinical and experimental reports suggest the possibility that antipruritic effects of selective serotonin reuptake inhibitors in atopic dermatitis patients might be at least partly due to their suppressive effect on T cells. Further studies should be conducted to elucidate the precise mechanism of neuroimmunological interaction in pruritus of atopic dermatitis.

• Biomolecules & Therapeutics
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• v.9 no.2
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• pp.88-95
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• 2001

(+)-Methamphetamine (METH) is a psychostimulant, which has been the most popular abused drug in Korea. The rewarding mechanism in METH abuse has been reported to be mediated by dopaminergic system. Recently, it has been reported that dopamine releaser (phentermine) plays a dominant role in the discriminative stimulus effects of METH, whereas 5-HT releaser (fenfluramine) can strongly modify METH self-administration. The present study is designed to assess the behavioral changes and the changes of the serotonin receptors in the brains of rats administered repeated of self-administered METH. The repeated administration of 1.0 mg/kg/day METH for 12 days increased locomotor activities, and there was no difference between i.v. and i.p. treatment. Rats had actively acquired METH self-administration for 3 weeks at 0.1 or 0.2 mg/kg/injection. Whereas, it was taken few days to acquire sucrose pellet self-administration. The binding of [$^3$H]-8-hydroxy-DPAT (5-H $T_{1A}$ receptors) and [$^3$H]-5-carboxytryptamine (5-H $T_{1B}$ receptors) to brain sections was examined. Both passive administration and self-administration of METH did not change significantly the serotonin receptors levels in hippocampus, striatum and nucleus accumbens. These results suggest that serotonin receptors may not change in the acquisition period of METH self-administration, and we are trying to investigate the serotonin receptors levels of brain in rats maintained of METH self-administration.n.n.

• YAKHAK HOEJI
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• v.55 no.2
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• pp.145-153
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• 2011

A simultaneous detection and quantification method for determining the Phenylalkylamine derivatives, such as methamphetamine (MA), amphetamine (AM), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), ketamine (KT), norketamine (NKT), phentermine (PT), fenfluramine (FFA) and phenmetrazine (PM), in oral fluid was developed and validated according to international guidelines. The validated method was applied to actual oral fluid samples collected from drug abuse suspects. The recovery of phenylalkylamines from oral fluid collection devices was also assessed. Oral fluid specimens from 20 drug abuse suspects submitted by the police were collected using Salivette$^{TM}$, Quantisal$^{TM}$ or direct expectoration. The samples were screened using a biochip array analyzer. For confirmation, the samples were analyzed by GC-MS in selected-ion monitoring (SIM) mode after extraction using automated SPE with a mixed-mode cation exchange cartridge and derivatization with trifluoroacetic anhydride (TFAA). The results from the immunoassay were consistent with those from GC-MS. All the oral fluid samples gave positive results for MA, AM, PT and/or PM. The detection of phenylalkylamines in oral fluid can provide a better indication of recent use than urine or hair. Therefore, the oral fluid specimen was useful for demonstrating phenylalkylamines abuse in the driving under the influence of drug (DUID) as an alternative specimen for urine.