• Environmental Analysis Health and Toxicology
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• 제27권
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• pp.7.1-7.7
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• 2012

Objectives: Modafinil is a waking drug prescribed to narcolepsy patients, but its usage among healthy individuals is increasing to enhance their alertness or to mitigate fatigue. This study was conducted to investigate practical use and toxic effects on neuro-immune interaction of modafinil. Methods: This study reviewed the significance of psychoactive drugs, and discussed the benefits and risks of the application of modafinil, which seems to be ideal as an anti-psychotic or anti-fatigue agent. Results: Modafinil is known to have less or no adverse effects than those found in traditional psychostimulants such as amphetamine, methylphenidate or cocaine. It can be applied as an anti-psychotic or anti-fatigue agent. However, the waking mechanism of modafinil is yet to be fully revealed. Recent studies reported that modafinil may be subject to abuse and addiction. In addition prolonged sleeplessness induces stress responses and impairs immune function. Conclusions: Modafinil can be used by anyone, who wishes to work late, stay awake, enhance their cognitive reactions, or brighten their moods. Users may already be under a great level of stress, i.e. cancer patients or soldiers in a battle field. A psychoneuroimmunological approach is thus needed to investigate the multi-functional effects of modafinil.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제33권2호
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• pp.27-34
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• 2022

Stimulants, such as amphetamine and methylphenidate, are one of the most effective treatment modalities for attention deficit hyperactivity disorder (ADHD) and may cause various movement disorders. This review discusses various movement disorders related to stimulant use in the treatment of ADHD. We reviewed the current knowledge on various movement disorders that may be related to the therapeutic use of stimulants in patients with ADHD. Recent findings suggest that the use of stimulants and the onset/aggravation of tics are more likely to be coincidental. In rare cases, stimulants may cause stereotypies, chorea, and dyskinesia, in addition to tics. Some epidemiological studies have suggested that stimulants used for the treatment of ADHD may cause Parkinson's disease (PD) after adulthood. However, there is still a lack of evidence that the use of stimulants in patients with ADHD may cause PD, and related studies are only in the early stages. As stimulants are one of the most commonly used medications in children and adolescents, close observations and studies are necessary to assess the effects of stimulants on various movement disorders, including tic disorders and Parkinson's disease.

• The Korean Journal of Physiology and Pharmacology
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• 제19권2호
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• pp.89-97
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• 2015

The aim of this study was to investigate the involvement of dopaminergic receptors (DR) in behavioral sensitization, as measured by locomotor activity, and the over-expression of cocaine- and amphetamine-regulated transcript (CART) peptides after repeated administration of cocaine in mice. Repeated administrations of cocaine induced behavioral sensitization and CART over-expression in mice. The levels of striatal CART mRNA were significantly increased on the $3^{rd}$ day. CART peptides were over-expressed on the $5^{th}$ day in the striata of behaviorally sensitized mice. A higher proportion of $CART^+$ cells in the cocaine-treated mice were present in the nucleus accumbens (NAc) shell than in the dorsolateral (DL) part of caudate putamen (CP). The concomitant administration of both $D_1R$ and $D_2R$ antagonists, SCH 23390 ($D_1R$ selective) and raclopride ($D_2R$ selective), blocked cocaine induced-behavioral sensitization, CART over-expression, and cyclic adenosine 5'-monophosphate (cAMP)/ protein kinase A (PKA)/phospho-cAMP response element-binding protein (pCREB) signal pathways. SCH 23390 more predominantly inhibited the locomotor activity, CART over-expression, pCREB and PKA activity than raclopride. Cocaine induced-behavioral sensitization was also attenuated in the both $D_1R$ and $D_2R$ knockout (KO) mice, respectively. CART over-expression and activated cAMP/PKA/pCREB signal pathways were inhibited in the $D_1R$-KO mice, but not in the $D_2R$-KO mice. It is suggested that behavioral sensitization, CART over-expression and activated cAMP/PKA/pCREB signal pathways induced by repeated administration of cocaine could be more predominantly mediated by $D_1R$.

• Biomolecules & Therapeutics
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• 제17권4호
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• pp.348-352
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• 2009

Over the last decade, the incidence of overweight and obesity has nearly doubled in many countries and is considered a pandemic. Obesity was identified as a major risk factor for cardiovascular disease as the same level as smoking and diabetes. Visceral fat is considered one of the key contributors to outcome and certain ethnic groups such as Asians seem to be more affected than others. Weight reduction through lifestyle changes was found to be impactful to improve overall health, but weight loss and maintenance thereof is limited and difficult to sustain. Surgical intervention demonstrated a greater weight loss in the severely obese and was associated with improved all-cause mortality. Despite numerous pharmacological targets and a high medical need, only few drugs have been successfully developed. Earlier studies with amphetamine-derived compounds showed significant weight loss but their critical safety profiles led to market withdrawals and disappointment. More recent compounds; orlistat - a lipase inhibitor, rimonabant - a cannaboid-1-receptor antagonist, and sibutramine - a combined serotonin/norepinephrine re-uptake inhibitor, all demonstrated similar significant efficacy; however, they carry specific safety profiles making them unsuitable for every patient. The main limitation of pharmacotherapy is the absence of clear benefit-risk assessments through outcome studies. Such a study - the SCOUT trial - was designed to compare sibutramine versus placebo and the effect on morbidity and mortality in nearly 10,000 obese patients with additional risk factors. Such studies could provide new scientific evidence for obesity treatment and may support future pharmacological approaches.

• Journal of Nutrition and Health
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• 제31권5호
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• pp.939-948
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• 1998

To investigate the relationship between eating behavior and the prevalence of adolescents drug abuse and smoking, this survey was conducted among 349 male students(mean age ; 16.0 $\pm$0.9yrs) at technical high schools in Kyunggi-Do. It was shown that 58.7% of total subjects were smoking and 11.2% were abusing drugs. Drug abusers weighed Less than non-abusers especially, student smokers were 2.7kg lighter than non-smokers despite the same height. Although parents' education showed no relationship with drug abuse, educational level of student smokers' fathers was significantly lower than that of non-smokers' fathers. Drug abusers and smokers showed significantly higher incidence of runaway from home, absence from school without notice, and parents' divorce than non-abusers and non-smokers. Drugs abused were sleeping pills(n=20), bonds and butane gas(n=9), marijuana(n=3), tranquilizer(n=3), morphine and cocaine(n=2), and pep pills like amphetamine(n=2) 76.9% of the drug abusers had their first experience in junior high school and 81% of the smokers stared smoking as early as in junior high school. Also, 44% of the smokers reported that they smoke daily. The drug abusers tended to have more irregular eating habits than the non-abusers. The smokers showed irregular mealtime, ate either too fast or too slow, and especially, often skipped lunch or dinner. The drug abusers and smokers took little vegetable in their meals and often ate bread or noodles instead of rice for staples. In addition, they preferred taste to nutrition when they had meals. The smokers tended to ingest smaller amount of calcium source such as milk or dinner food and fish with bone although they consume more volume of total foods than the non-smokers. All subjects took less in calorie, calcium, iron, vitamin A, vitamin E, riboflavin, and folic acid than the Recommended Dietary Allowance Those findings suggest that drug abuse and smoking cause bad eating habits that influence unbalanced nutritional state. Therefore, nutrition education should be provided to the adolescents so that they can recognize the disadvantages of drug and smoking and its relation to dietary relation. (Korean J Nutrition 31(5) : 939-948, 1998)

• Nutritional Sciences
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• 제9권2호
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• pp.61-67
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• 2006

Green tea has attracted attention with respect to its potential for preventing and treating neurodegenerative disease. The neurotoxin, 6-hydroxydopamine (6-OHDA), was used to produce experimental Parkinson's disease (PD) model. The purpose of this study was to investigate the effects of green tea diet on behavioral changes, striatal dopamine content, and hepatic antioxidant parameters of PD model rats. In this study, we used male Sprague-Dawley rats weighing $200\sim220g$ and injected 6-OHDA into the right substantia nigra and medial forebrain bundle of the brain. The supply of green tea diet was started at 2 weeks before 6-OHDA lesion and continually supplied during 0, 2, and 4 weeks after 6-OHDA lesion (GT-0, GT-2, GT-4). Behavioral disturbance was measured by the stepping and d-amphetamine drug-induced rotation tests. Then, we assayed the striatal dopamine content and the hepatic malondialdehyde (MDA), hydrogen peroxide $(H_2O_2)$, and superoxide dismutase (SOD) activity. The percentage of lesioned forepaw to non-lesioned forepaw step scores was the highest in GT-4 group among all groups at both 3 and 4 weeks after 6-OHDA lesion. At 4 weeks after 6-OHDA lesion, the rotation score was the lowest in GT-2 group (p<0.05). However, increasing rate of the rotation score from 2 to 4 weeks after 6-OHDA lesion was the lowest in GT-4 group. The striatal dopamine content was not significantly different among four groups by green tea diet. The hepatic MDA level was the lowest in GT-4 group among four groups. The hepatic SOD activity was increased with the prolongation of green tea diet period These results suggest that green tea diet affects behavioral changes in rats of PD model. It seems that continuous green tea supplementation has an influence on the reduction of behavioral disturbance and the hepatic MDA level. Accordingly, continuous green tea supplementation was recommended for the prevention and treatment of PD. However, further studies are needed to investigate the mechanisms and efficacy of green tea in PD.

• Biomolecules & Therapeutics
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• 제19권1호
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• pp.45-51
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• 2011

These experiments were designed to use typical makers from behaviors and molecular basis in addicted animals of morphine and cocaine. Morphine has been widely abused with a high physical dependence liability. Morphine withdrawal activates the intracellular cAMP signaling pathway and further leads to changes in the expression of the cAMP response element binding protein (CREB), which may be important to the development and expression of morphine dependence. From these experiments, repeated morphine (10 mg/kg, twice per day for 7 days) developed physical dependence. Withdrawal signs were precipitated by naloxone and also increased the expression of the CREB. In addition, repeated exposure of cocaine (15 mg/kg) to mice develops locomotor sensitization and produced lasting behavioral sensitivity. Cocaine- and amphetamine-regulated transcript peptide (CART) peptide was up-regulated by repeated administration of cocaine in the striatum. Therefore, repeated morphine induced the development of physical dependence and increased pCREB. In addition, repeated cocaine induced locomotor sensitization and over-expressed CART peptide. In conclusion, the development of physical dependence and pCREB for morphine, and locomotor sensitization and CART peptide over-expression for cocaine would be useful markers to predict the abuse potential of opioid analgesics and pychostimulant drugs in animals, respectively.

• 약학회지
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• 제55권2호
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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.

• 대한약리학회지
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• 제11권2호
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• pp.19-27
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• 1975

Haloperidol, a butyrophenone, was synthetized by Janssen and introduced for the treatment of psychosis. Although structurally different from the phenothiazines, the butyrophenones share many of their pharmacological properties, such as inhibition of conditioned avoidance response, blocking effect of amphetamine reaction, producing catalepsy, antishock effect and protection against the lethal effects of catecholalmines. Chlorpromazine can lower the arterial blood pressure through its adrenergic blocking activity, its direct effect in relaxing vascular smooth muscle, its direct effect in depressing the myocardium and its action in a complex manner on the central nervous system. In the case of haloperidol, however, was not clarified the mechanism of lowering the blood pressure. The present paper describes the effects of haloperidol on cardiovascular system to investigate the mechanisms of its actions on the arterial blood pressure. The results are followings; 1. In anesthetized cats, intravenous administration of haloperidol and chlorpromazine in the dose of 0.1mg/kg produced a slight decrease in the blood pressure, which followed by complete recovery within $30{\sim}60$ minutes. In the dose of 3mg/kg, however, both produced an abrupt and marked decrease of the blood pressure, which followed by delayed recovery. 2. Haloperidol in the dose ranges of 0.1mg to 3.0mg/kg tended to produce the heart rate slowing in the cats, while chlorpromazine has no effect on the rate. 3. Following administration of haloperidol or chlorpromazine, epinephrine reversal in the arterial blood pressure was observed in the cat, however the responses of norepinephrine and acetylcholine were little affected. 4. In the isolated rabbit atrium the contractility was depressed by haloperidol in the doses over 0.5mg per 100ml, but the rate was not affected. In contrast, the epinephrine-induced contractility was not depressed after haloperidol treatment. However, the increased rate of atrium by epinephrine was partially blocked after haloperidol. 5. In the isolated rabbit aortic strip, epinephrine-induced contraction was blocked by haloperidol. With the above results, it may be concluded that the hypotensive effect of haloperidol was largely due to ${\alpha}$-adrenergic blocking properties and the direct effect in depressing the myocardium as well as its action on central nervous system.

• The Korean Journal of Physiology and Pharmacology
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• 제13권2호
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• pp.71-78
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• 2009

(S)-Carbamic acid 2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-1-phenyl-ethyl ester hydrochloride (YKP1447) is a novel "atypical" antipsychotic drug which selectively binds to serotonin (5-$HT_{2A}$, Ki=0.61 nM, 5-$HT_{2C}$, Ki=20.7 nM) and dopamine ($D_2$, Ki=45.9 nM, $D_3$, Ki=42.1 nM) receptors with over $10\sim100$-fold selectivity over the various receptors which exist in the brain. In the behavioral studies using mice, YKP1447 antagonized the apomorphine-induced cage climbing ($ED_{50}$=0.93 mg/kg) and DOI-induced head twitch ($ED_{50}$=0.18 mg/kg) behavior. In the dextroamphetamine-induced hyperactivity and conditioned avoidance response (CAR) paradigm in rats, YKP1447 inhibited the hyperactivity induced by amphetamine ($ED_{50}$=0.54 mg/kg) and the avoidance response ($ED_{50}$=0.48 mg/kg); however, unlike other antipsychotic drugs, catalepsy was observed only at much higher dose ($ED_{50}$=68.6 mg/kg). Based on the CAR and catalepsy results, the therapeutic index (TI) value for YKP1447 is over 100 (i.p.). These results indicate that YKP1447 has an atypical profile and less undesirable side effects than currently available drugs.