A precision medication study of atomoxetine in children with attention deficit hyperactivity disorder: CYP2D6 genetic testing and therapeutic drug monitoring / 中国当代儿科杂志

Atomoxetine is the first non-stimulant drug for the treatment of children and adults with attention deficit hyperactivity disorder (ADHD), and its safety and efficacy show significant differences in the pediatric population. This article reviews the genetic factors influencing the pharmacokinetic differences of atomoxetine from the aspect of the gene polymorphisms of the major metabolizing enzyme CYP2D6 of atomoxetine, and then from the perspective of therapeutic drug monitoring, this article summarizes the reference ranges of the effective concentration of atomoxetine in children with ADHD proposed by several studies. In general, there is an association between the peak plasma concentration of atomoxetine and clinical efficacy, but with a lack of data from the Chinese pediatric population. Therefore, it is necessary to establish related clinical indicators for atomoxetine exposure, define the therapeutic exposure range of children with ADHD in China, and combine CYP2D6 genotyping to provide support for the precision medication of atomoxetine.

Synergisms of cardiovascular effects between iptakalim and amlodipine, hydrochlorothiazide or propranolol in anesthetized rats / 中国应用生理学杂志

The primary object of this fundamental research was to survey the synergistic cardiovascular effects of iptakalim, a novel ATP-sensitive potassium channel (K(ATP)) opener, and clinical first-line antihypertensive drugs, such as calcium antagonists, thiazide diuretics and β receptor blockers by a 2 x 2 factorial-design experiment. It would provide a theoretical basis for the development of new combined antihypertensive therapy program after iptakalim is applied to the clinic. Amlodipine besylate, hydrochlorothiazide and propranolol were chosen as clinical first-line antihypertensive drugs. Blood pressure, heart rate (HR) and cardiac functions were observed in anesthetized normal rats by an eight-channel physiological recorder. The results showed that iptakalim monotherapy in a low dose could produce significant antihypertensive effect. There was no interaction between iptakalim and amlodipine on the maximal changes of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP), the left ventricular systolic pressure (LVSP), and the left ventricular end-diastolic pressure (LVEDP) (P > 0.05). However, the effects of combination iptakalim/amlodipine on the maximal changes of SBP, DBP, MABP, LVSP and LVEDP were more obvious than those of iptakalim or amlodipine monotherapy. And there was strong positive interaction between iptakalim and amlodipine on the maximal changes of HR (P>0.05). According to the maximal changes of DBP, MABP, LVSP and LVEDP (P < 0.05) of combination iptakalim with hydrochlorothiazide, there was strong positive interaction between them. But there was no interaction between iptakalim and hydrochlorothiazide on the maximal drop of SBP and HR (P > 0.05). According to the maximal drops of DBP, MABP of combination iptakalim with propranolol, there was strong positive interaction between them (P < 0.05). But there was no interaction between iptakalim and propranolol on the maximal changes of SBP, LVSP, LVEDP and HR (P > 0.05). In conclusion, it was the first time to study the effects of amlodipine, hydrochlorothiazide or propranolol, which had different mechanisms of action from iptakalim, on cardiovascular effects of iptakalim in anesthetized normal rats. This study proved that the combination of iptakalim with hydrochlorothiazide or propranolol respectively had significant synergism on lowering blood pressure, while the combination of iptakalim/amlodipine had additive action on lowering blood pressure. Meanwhile the antihypertensive effect was explicit, stable and long-lasting. Iptakalim thus appears suitable for the clinical treatment of hypertensive people who need two or more kinds of antihypertensive agents.

The selective dilatation effects of iptakalim on basilar and pulmonary arterioles in high-altitude hypoxic rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the selective dilatation effects of iptakalim (Ipt) on basilar and pulmonary arterioles, and endothelial cell function of these arterioles in hypoxic rats.</p><p><b>METHODS</b>SD male rats were divided into 2 groups:control and hypoxic group fed in normobaric hypoxic environment (O2 7.8%, 8 h). Arteriole rings about (204 + 5) pm were isolated and the tension of hypoxic arterioles pre-contracted by 6 nmol/L endothelin-1 (ET-1) was observed with wire myograph system model (DMT 610 m). The relaxing response of hypoxic arterioles induced by different concentration of Ipt were detected and endothelial activity was also tested by acetylcholine.</p><p><b>RESULTS</b>10(5) mol/L acetylcholine (ACh)-mediated vasodilatation of basilar and pulmonary arterioles was greatly reduced in the hypoxic group than those in control group (P < 0.05). Compared with normal group, a novel ATP-sensitive potassium channel opener Ipt at the concentration ranging from 10(-11) mol/L to 10(3) mol/L, caused stronger dose dependent vasodilatation on hypoxic pulmonary arterioles, and there was no significant difference between control and hypoxic basilar arterioles.</p><p><b>CONCLUSION</b>The endothelial function of basilar and pulmonary arterioles was damaged under hypoxic state, and Ipt selectively increased dilatation effects on hypoxic pulmonary arterioles, but not on hypoxic basilar arterioles which could improve high altitude pulmonary edema pathological state and be the novel drug in the treatment of pulmonary hypertension.</p>

Multi Target Neuroprotective and Neurorestorative Anti-Parkinson and Anti-Alzheimer Drugs Ladostigil and M30 Derived from Rasagiline

Present anti-PD and -AD drugs have limited symptomatic activity and devoid of neuroprotective and neurorestorative property that is needed for disease modifying action. The complex pathology of PD and AD led us to develop several multi-target neuroprotective and neurorestorative drugs with several CNS targets with the ability for possible disease modifying activity. Employing the pharmacophore of our anti-parkinson drug rasagiline (Azilect, N-propagrgyl-1-R-aminoindan), we have developed a series of novel multi-functional neuroprotective drugs (A) [TV-3326 (N-propargyl-3R-aminoindan-5yl)-ethyl methylcarbamate)], with both cholinesterase-butyrylesterase and brain selective monoamine-oxidase (MAO) A/B inhibitory activities and (B) the iron chelator-radical scavenging-brain selective monoamine oxidase (MAO) A/B inhibitor and M30 possessing the neuroprotective and neurorescuing propargyl moiety of rasagiline, as potential treatment of AD, DLB and PD with dementia. Another series of multi-target drugs (M30, HLA-20 series) which are brain permeable iron chelators and potent selective brain MAO inhibitors were also developed. These series of drugs have the ability of regulating and processing amyloid precursor protein (APP) since APP and alpha-synuclein are metaloproteins (iron-regulated proteins), with an iron responsive element 5"UTR mRNA similar to transferring and ferritin. Ladostigil inhibits brain acetyl and butyrylcholinesterase in rats after oral doses. After chronic but not acute treatment, it inhibits MAO-A and -B in the brain. Ladostigil acts like an anti-depressant in the forced swim test in rats, indicating a potential for anti-depressant activity. Ladostigil prevents the destruction of nigrostriatal neurons induced by infusion of neurotoxin MPTP in mice. The propargylamine moiety of ladostigil confers neuroprotective activity against cytotoxicity induced by ischemia and peroxynitrite in cultured neuronal cells. The multi-target iron chelator M30 has all the properties of ladostigil and similar neuroprotective activity to ladostigil, but is not a ChE inhibitor. M30 has a neurorestorative activity in post-lesion of nigrostriatal dopamine neurons in MPTP, lacatcystin and 6-hydroxydopamine animal models of PD. The neurorestorative activity is related to the ability of the drug to activate hypoxia inducing factor (HIF) which induces the production of such neurotrophins as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and erythropoietin as well as glia-derived neurotrophic factor (GDNF). The unique multiple actions of ladostigil and M30 make the potentially useful drugs for the treatment of dementia with Parkinsonian-like symptoms and depression.

Use of Atypical Antipsychotics in Attention-Deficit Hyperactivity Disorder / 대한정신약물학회지

Psychopharmacotherapy is one of the effective treatments for the children and adolescents with attention-deficit hyperactivity disorder (ADHD). If there were a marginal improvement or significant adverse effects after having the first line medication such as psychostimulants and atomoxetine, the youth with ADHD can take alternative medications. If they have comorbidities such as disruptive behavior disorder, bipolar disorder, mental retardation and tic disorder, they need to have more medications. Recently, prescriptions of atypical antipsychotics were increasing among them. The efficacy, safety, and tolerability of atypical antipsychotics in the youth should be considered.

Effects of ATP-sensitive potassium channel opener iptakalim against ventricular remodeling and its mechanisms of endothelial protection / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the effects of iptakalim (Ipt), an ATP-sensitive potassium channel opener, on cardiac remodeling induced by isoproterenol (ISO) in Wistar rats.</p><p><b>METHODS</b>ISO was given subcutaneously (85 mg/(kg x d), sc, 7 days) to induce cardiac remodeling in rats. The rats in Ipt treated group were administrated with Ipt 3 mg/kg (po) after ISO injection. After treated with Ipt for 6 weeks, the hemodynamic parameters were tested by an eight channel physiological recorder (RM-6000). Then the heart weight was weighed and the cardiac remodeling index was calculated. HE stain and Masson's stain were employed to perform histological analysis, the hydroxyproline(Hyp) content in cardiac tissue was detected by colorimetric method, radioimmunoassay was used to measure the plasma levels of endothelin-1 (ET-1) and prostacyclin (PGI2).</p><p><b>RESULTS</b>Six weeks after ISO injection, the cardiac functions of model group were damaged markedly compared with those of normal group. The characteristics of ventricular remodeling in model group included that the heart weight index, myocyte cross-sectional area, myocardial fibrosis, and the hydroxyproline content in cardiac tissue were all increased significantly. The plasma level of ET-1 was increased, while the plasma level of PGI2 was decreased significantly. These changes could be reversed by Ipt treatment (3 mg/(kg x d) for 6 weeks).</p><p><b>CONCLUSION</b>Ipt can reverse cardiac remodeling induced by isoproterenol in rats. The endothelial protective effect regulating effects of Ipt on the balance between the ET-1 and PGI2 system may be involved in its mechanisms.</p>

The selective dilatation effects of iptakalim on pulmonary arterioles in hypoxic pulmonary hypertensive rat / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the selective dilatation effects of iptakalim (Ipt), a novel ATP-sensitive potassium channel opener, on pulmonary arterioles in hypoxic pulmonary hypertensive rat.</p><p><b>METHODS</b>SD male rats were divided into 3 groups, control group, the rest were fed in hypoxic and normobaric environment (O2 10% +/- 0.5%, 8 h/d and 6 d/week) and divided into hypoxia group and hypoxia plus acetazolamide (Acz) group (hypoxic rats were treated with ig acetazolamide (Acz) 80 mg x kg(-1) d(-1)) . After 12 weeks, pulmonary arteriole rings about (197 +/- 4) microm were isolated and the tension of hypoxic pulmonary arterioles pre-contracted by 6 nmol/L endothelin-1 (FT-1) was observed with wire myograph system model (DMT 610 m). The relaxing response of hypoxic pulmonary arterioles induced by different concentration of Ipt were detected and endothelial activity was also tested by acetylcholine.</p><p><b>RESULTS</b>10(-5) mol/L acetylcholine (ACh)-mediated vasodilatation was greatly reduced in the hypoxic group than those in control group (P < 0.01) and there was no significant difference between Acz treatment group and control group (P > 0.05). Ipt at the concentration ranging from 10(-11) mol/L to 10(-4) mol/L, caused dose dependent vasodilation on both hypoxic pulmonary arterioles and Acz treatment group (P > 0.05), but not on normal group.</p><p><b>CONCLUSION</b>The endothelial function of pulmonary arterioles was damaged under hypoxic pulmonary hypertensive state, and Ipt showed selective dilatation effects on hypoxic pulmonary arterioles. Acz could improve the dysfunction of endothelial cells induced by hypoxic pulmonary hypertensive state, which didn't affect the selective dilatation effects of Ipt on hypoxic pulmonary arterioles.</p>

Screening of functional components derived from fresh water laver, Prasiola japonica, and its pharmacological properties / 동물의과학연구지

The aim of the current study was to analyze the active ingredients and to screen the pharmacological properties of freshwater laver, Prasiola japonica, the only species grown in Korea. According to results of gas chromatography-mass spectrometry assay, components from P. japonica were more diverse than those from sea laver. Of particular interest, our results indicated that ethanol extract of P. japonica (PJE) contained loliolide, sorbitol, mannitol, and alverine, which were known to have an anti-oxidant, anti-oral microbial, osmotic diuresis, and smooth muscle relaxant, respectively. In addition, five solvent fractions of PJE (water, butanol, chloroform, ethyl acetate, and hexane) significantly inhibited the production of lipopolysaccharide-induced nitric oxide and a higher amount (>100 microg/mL) of chloroform, ethyl acetate, and hexane fraction were considered to play a specific role in cancer cell death. PJE and its solvent fractions found to be effective scavengers of free radicals, particularly, hydroxyl radicals. Glucose uptake in L6 myoblast cell line that stably expresses the glucose transporter type 4 (GLUT4) proteins was also remarkably enhanced upon treatment with solvent fractions, remarkably chloroform fraction. Taken together, we concluded that P. japonica may have potent pharmacological properties and thus contribute to development of novel natural candidates for various disease targets.

Evaluación de la efectividad y seguridad de la atomoxetina para déficit atencional en población entre 6 y 19 años: revisión sistemática / Effectiveness and safety of atomoxetine for ADHD in population between 6 and 19 years: a systematic review

Introducción: el Trastorno por déficit de atención e hiperactividad (TDAH) dispone de intervenciones farmacológicas como los psicoestimulantes. El más usado es el metilfenidato y posteriormente se ha incluido la atomoxetina. Objetivo: identificar, sintetizar y evaluar la mejor evidencia disponible sobre la efectividad y seguridad de la atomoxetina en el tratamiento en déficit atencional en la población de 6 a 19 años. Métodos: se realizó una revisión sistemática de estudios de intervenciones, que evaluaron efectividad comparada de atomoxetina con placebo y metilfenidato. Las medidas fueron funcionamiento educacional, funcionamiento psicosocial, calidad de vida y efectos adversos. Se consultó en bases de datos hasta febrero de 2012 en inglés y castellano: PubMed, LILACS, Cochrane, DARE y National Guideline Clearinghouse. Los artículos incluidos fueron evaluados por dos investigadores en forma independiente. Resultados: de los 108 estudios encontrados inicialmente, se incluyeron 11, entre ellos 5 revisiones sistemáticas, un artículo primario y 5 guías clínicas. Conclusiones: la atomoxetina se recomienda como segunda opción en el TDAH por ser superior al placebo, cuando falla el metilfenidato o hay presencia de comorbilidades.

Introduction: Attention deficit hyperactivity disorder (ADHD) is generally treated with pharmacological interventions such as psychostimulants. The most used widely used one is methylphenidate followed by atomoxetine. Purpose: To identify, synthesize and evaluate the best available evidence on the effectiveness and safety of atomoxetine in ADHD treatment in the 6-19 year-old population. Methods: A systematic review of intervention studies that evaluated effectiveness of atomoxetine compared with placebo and methylphenidate was conducted. Outcomes assessed were educational functioning, psychosocial functioning, quality of life and adverse effects. The search was done up to February 2012 in English and Spanish in the following databases: PubMed/MEDLINE, LILACS, Cochrane, DARE and National Guideline Clearinghouse. The articles were independently evaluated by two investigators. Results: Of the 108 studies found initially, 11 were included, among which five systematic reviews, one primary article and 5 clinical guidelines. Conclusions: Atomoxetine is recommended as a second option in ADHD and was found to be superior to placebo. Its use is recommended when methylphenidate fails or comorbidities are present.

open clinical study of immediate release methylphenidate [IR-MPH] versus atomoxetine [ATX] in attention deficit hyperactivity disorder

Studies that focus on treatment efficacy with an effectiveness study design provide the best evidence for the practicing clinician regarding the usefulness of treatment methods. The present study was carried out to evaluate the effectiveness and tolerability of Methylphenidate [MPH] versus Atomoxetine [ATX] in children aged 8 to 12 years with ADHD. Open label clinical study. Private psychiatric centre in Mumbai over a period of 2 years from January 2007 to January 2009. This 12 week, open-label study had 183 subjects on either MPH or ATX. Subjects were titrated to a clinically effective dose of either study medication over 4 weeks and maintained on that dose for an additional 8 weeks. The SNAP-IV parent-rating scale was the primary effective measure used in the study. Other measures used was the Conners Parent rating Scale, Parent Stress Index, IOWA Parent Rating Scale and the Clinical Global Impression Scale for severity and improvement. MPH showed statistically significant superiority to ATX based on the 18 ADHD symptoms of the SNAP-IV [p = 0.01] and severity of ADHD and ODD symptoms [p=0.008] as well as on the following secondary assessments. Parental stress too was lower in the MPH group [p = 0.007]. Both drugs were well tolerated with a similar side effect profile. The study concluded that MPH is significantly more effective than ATX in reducing ADHD symptoms based on multiple outcome measures in this study group though further studies across different populations are warranted

Effect of iptkalim on myocardial enzymes and free radicals metabolism with hypoxic pulmonary hypertension / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the effects of iptkalim on myocardial enzymes and free radicals metabolism with hypoxic pulmonary hypertension (HPH), in order to provide evidence for the mechanism of iptkalim on clinical treat.</p><p><b>METHODS</b>110 young men stayed at high altitude above 5 000 m were divided into iptkalim group (n = 74) and placebo group (n = 36), aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (gamma-GT), creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), malonaldehyde (MDA), nitric oxide(NO) and nitric oxide synthase(NOS) were detected before and after took medicines for 6 mouths.</p><p><b>RESULTS</b>After took medication for 6 mouths, ALT, AST, gamma-GT, CK and LDH were reduced, SOD, NO, and NOS were increased, MDA were reduced, there were very significant difference (P < 0.05).</p><p><b>CONCLUSION</b>Oxygen free radicals have taken part in the process of HPH, iptkalim have the effect of anti-peroxidation of lipid and protect myocardial cells stress injured by hypoxia which related with mitochondrial membrane and cell membrane's K(ATP) channel activation.</p>

Hypoxic pulmonary hypertension and novel ATP-sensitive potassium channel opener: the new hope on the horizon / 中国应用生理学杂志

Hypoxic pulmonary hypertension (HPH) is a syndrome characterized by the increase of pulmonary vascular tone and the structural remodeling of peripheral pulmonary arteries. The aim of specific therapies for hypoxic pulmonary hypertension is to reduce pulmonary vascular resistance, reverse pulmonary vascular remodeling, and thereby improving right ventricular function. Iptakalim, a lipophilic para-amino compound with a low molecular weight, has been demonstrated to be a new selective ATP-sensitive potassium (K(ATP)) channel opener via pharmacological, electrophysiological, biochemical studies, and receptor binding tests. In hypoxia-induced animal models, iptakalim decreases the elevated mean pressure in pulmonary arteries, and attenuates remodeling in the right ventricle, pulmonary arteries and airways. Furthermore, iptakalim has selective antihypertensive effects, selective vasorelaxation effects on smaller arteries, and protective effects on endothelial cells, but no effects on the central nervous, respiratory, digestive or endocrine systems at therapeutic dose. Our previous studies demonstrated that iptakalim inhibited the effects of endothelin-1, reduced the intracellular calcium concentration and inhibited the proliferation of pulmonary artery smooth muscle cells. Since iptakalim has been shown safe and effective in both experimental animal models and phase I clinical trials, it can be a potential candidate of HPH in the future.

Activation of SUR2B/Kir6.1-type K(ATP) channels protects glomerular endothelial, mesangial and tubular epithelial cells against oleic acid renal damage / 中国应用生理学杂志

Cumulative evidence suggests that renal vascular endothelial injury play an important role in initiating and extending tubular epithelial injury and contribute to the development of ischemic acute renal failure. Our previous studies have demonstrated that iptakalim's endothelium protection is related to activation of SUR2B/Kir6.1 subtype of ATP sensitive potassium channel (K(ATP)) in the endothelium. It has been reported that SUR2B/Kir6.1 channels are widely distributed in the tubular epithelium, glomerular mesangium, and the endothelium and the smooth muscle of blood vessels. Herein, we hypothesized that activating renal K(ATP) channels with iptakalim might have directly neroprotective effects. In this study, glomerular endothelial, mesangial and tubular epithelial cells which are the main cell types to form nephron were exposed to oleic acid (OA) at various concentrations for 24 h. 0.25 microl/ml OA could cause cellular damage of glomerular endothelium and mesangium, while 1.25 microl/ml OA could lead to the injury of three types of renal cells. It was observed that pretreatment with iptakalim at concentrations of 0.1, 1, 10 or 100 micromol/L prevented cellular damage of glomerular endothelium and tubular epithelium, whereas iptakalim from 1 to 100 micromol/L prevented the injury of mesangial cells. Our data showed iptakalim significantly increased survived cell rates in a concentration-dependent manner, significantly antagonized by glibenclamide, a K(ATP) blocker. Iptakalim played a protective role in the main cell types of kidney, which was consistent with natakalim, a highly selective SUR2B/Kir6.1 channel opener. Iptakalim exerted protective effects through activating SUR2B/Kir6.1 channels, suggesting a new strategy for renal injury by its endothelial and renal cell protection.

Protective effects of SUR2B/Kir6.1 potassium channel opener natakalim against RAVECs injuries induced by hypoxia / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the protective effects of natakalim against rat aortic vascular endothelial cells (RAVECs) injuries induced by hypoxia and its mechanisms.</p><p><b>METHODS</b>Selecting RAVECs as a cell model injured by hypoxia, these RAVECs were divided into 5 groups: i.e. control group, hypoxia group, natakalim low, medium and high group. The cell survival rate was determined by MTT assay, con was measured using Griess Assay, RT-PCR was used to examine t he expression of intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1) mRNA in RAVEC.</p><p><b>RESULTS</b>Natakalim could reverse hypoxia-induced changes in endothelial cell function, including increased endothelial cell survival rate and level of NO concentration, significantly inhibited the hypoxia-induced endothelial ICAM-1, ET-1, VEGF mRNA expression levels increased.</p><p><b>CONCLUSION</b>Natakalim have protective effects on hypoxia-induced changes in endothelial cell function, increasing of permeation, excess expression of cell adhesion molecules.</p>

Iptakalim Preferentially Decreases Nicotine-induced Hyperlocomotion in Phencyclidine-sensitized Rats: A Potential Dual Action against Nicotine Addiction and Psychosis

OBJECTIVE: Iptakalim is a putative ATP-sensitive potassium (KATP) channel opener. It is also a novel nicotinic acetylcholine receptor (nAChR) blocker and can antagonize nicotine-induced increase in dopamine release in the nucleus accumbens. Our recent work also shows that iptakalim exhibits a clozapine-like atypical antipsychotic profile, indicating that iptakalim may possess a dual action against nicotine addiction and schizophrenia. METHODS: The present study examined the potential therapeutic effects of iptakalim on nicotine use in schizophrenia. We created an animal model of comorbidity of nicotine addiction and schizophrenia by injecting male Sprague-Dawley rats with nicotine (0.40 mg/kg, subcutaneously[sc]) or saline, in combination with phencyclidine (PCP, 3.0 mg/kg, sc) or saline daily for 14 consecutive days. RESULTS: During the PCP/nicotine sensitization phase, PCP and nicotine independently increased motor activity over time. PCP also disrupted prepulse inhibition (PPI) of acoustic startle response. Acute nicotine treatment attenuated the PCP-induced hyperlocomotion and PCP-induced disruption of PPI, whereas repeated nicotine treatment potentiated these effects. Importantly, pretreatment with iptakalim (10-20 mg/kg, intraperitoneally) reduced nicotine-induced hyperlocomotion in a dose-dependent fashion. This reduction effect was highly selective: it was more effective in rats previously sensitized to the combination of PCP and nicotine, but less effective in rats sensitized to saline, nicotine alone or PCP alone. CONCLUSION: To the extent that the combined nicotine and PCP sensitization mimics comorbid nicotine addiction in schizophrenia, the preferential inhibitory effect of iptakalim on nicotine-induced hyperlocomotion suggests that iptakalim may be a potential useful drug for the treatment nicotine abuse in schizophrenia.

Treatment for Attention-Deficit/Hyperactivity Disorder in Adults

This review examined the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults. It briefly addresses the issues about the cause of hospital visit, diagnosis, and impact of disease, specific to adults. The article focused on the evidence regarding the efficacy and tolerability of short- and long-acting stimulant medications, as well as the non-stimulant medications such as atomoxetine and bupropion in the treatment of the adult ADHD. Generally speaking, variability in diagnostic criteria, dosing parameters and response rates between the various studies were considerable. The aggregated literature shows that both the stimulants and non-stimulants had clinically significant beneficial effect on treating ADHD in adults. Special attention is given to the pharmacological treatment for patients with adult ADHD and various comorbidities. In summary, medications are effective and combined medication and psychosocial treatment is the most beneficial treatment option for most adult patients with ADHD.

Treatment for Attention-Deficit/Hyperactivity Disorder in Adults

This review examined the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults. It briefly addresses the issues about the cause of hospital visit, diagnosis, and impact of disease, specific to adults. The article focused on the evidence regarding the efficacy and tolerability of short- and long-acting stimulant medications, as well as the non-stimulant medications such as atomoxetine and bupropion in the treatment of the adult ADHD. Generally speaking, variability in diagnostic criteria, dosing parameters and response rates between the various studies were considerable. The aggregated literature shows that both the stimulants and non-stimulants had clinically significant beneficial effect on treating ADHD in adults. Special attention is given to the pharmacological treatment for patients with adult ADHD and various comorbidities. In summary, medications are effective and combined medication and psychosocial treatment is the most beneficial treatment option for most adult patients with ADHD.

A Randomized, Open-Label Assessment of Response to Various Doses of Atomoxetine in Korean Pediatric Outpatients with Attention-Deficit/Hyperactivity Disorder

OBJECTIVE: This multicenter, randomized, open-label, parallel trial aimed to provide a detailed dose-response profile for atomoxetine in Korean pediatric outpatients with attention-deficit/hyperactivity disorder (ADHD). METHODS: Male and female outpatients aged 6-18 years with ADHD meeting symptom severity criteria of 1.5 standard deviations above age and gender norms on the ADHD Rating Scale-IV-Parent: Investigator-Administered and Scored (ADHDRS-IV-Parent: Inv), and a Clinical Global Impression-ADHD-Severity score > or =4 were randomized to atomoxetine (mg/kg/day) 0.2 fixed, 0.5 fixed or 0.5 (7 days), 0.8 (7 days) then 1.2 for 28 days. The primary efficacy measure was change in ADHDRS-IV-Parent: Inv total score after 6 weeks of atomoxetine treatment. RESULTS: Of 153 randomized patients, 83.7% were male and mean age was 9.8 (SD+/-2.4) years. The completion rate was 86.9%. A graded dose response was apparent with mean change in ADHDRS-IV-Parent: Inv total scores of -9.6, -12.3 and -14.5 with atomoxetine 0.2, 0.5 and 1.2 mg/kg/day, respectively (p=0.024 - F-test). Moreover, a greater reduction in ADHD symptoms, as assessed by mean change from baseline to endpoint CGI-S and mean CGI-ADHD-Improvement at endpoint, was also observed with increasing atomoxetine dose. More patients receiving atomoxetine 1.2 mg/kg/day reported > or =1 treatment-emergent adverse event/s (58.3%) compared with 0.5 (40.7%; p=0.11) or 0.2 mg/kg/day (29.4%; p=0.005). These were generally mild to moderate. CONCLUSION: Atomoxetine was found to be safe and well tolerated at all doses administered in Korean pediatric ADHD patients, and 1.2 mg/kg/day was an efficacious dose in this population.

Effects of iptakalim on pressure-overload induced cardiac remodeling and plasma PGI2 content in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the effects of iptakalim (IPT) on pressure-overload induced cardiac remodeling in rats, and investigate correlation between this protection effects and plasma PGI2 content.</p><p><b>METHOD</b>The pressure-overload induced cardiac remodeling model was induced by abdominal aorta constriction for 6 weeks, and the rats were divided into 5 groups repectively: (1) sham group, (2) control group, (3) IPT 3 mg/kg group (IPT 3), (4) indomethacin 2 mg/kg group (Indo 2), (5) indomethacin 2 mg/kg + IPT 3 mg/kg group (Indo 2 + IPT 3). RM6000 eight channel physiological recorder was used to record haemodynamics index, heart weight was weighed and the cardiac remodeling index was calculated, HE stain and Masson's stain were employed to perform histological analysis, colorimetric method was used to detect the hydroxyproline content in cardiac tissue, radioimmunological method was used to measure the plasma PGI2 content.</p><p><b>RESULTS</b>After 42 days of aortic banding, the hyperdynamic circulation state, cardiac remodeling and decreased plasma PGI2 content were observed in the model group compared with those in the sham group, which were effectively reserved by treatment with IPT 3 mg/kg. Single-use indomethacin led to further deterioration of this pathophysiological changes, however, combination administration of IPT 3 mg/kg prevented these from worsening characteristic by ameliorating hyperdynamic circulation state and cardiac remodeling, augmnent plasma PGI2 content.</p><p><b>CONCLUSION</b>IPT can significantly reverse abdominal aorta binding/pressure-overload induced cardiac remodeling, its mechanism may contribute to binding K(ATP) channel in endothelial cells, ameliorating endothelium cells function, augmenting PGI2 synthesis and secretion.</p>

Effectiveness and safety of methylphenidate and atomoxetine for attention deficit hyperactivity disorder: a systematic review / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To assess and compare the effectiveness and safety of methylphenidate immediate-release tablets (IR-MPH), methylphenidate controlled release tablets (OROS-MPH) and atomoxetine (AHC) for attention deficit hyperactivity disorder (ADHD) in Chinese children.</p><p><b>METHODS</b>Randomized or clinical controlled trials on the effectiveness and safety of IR-MPH, OROS-MPH and AHC for ADHD were searched in electronic databases of CNKI, VIP, CBMDISC online, PubMed, Embase and MEDLINE. Two reviewers independently extracted the data and assessed the quality of the included literatures.</p><p><b>RESULTS</b>Eight trials were finally included. IR-MPH, OROS-MPH and AHC were effective for ADHD. OROS-MPH was superior to IR-MPH in the improvement of peer relationship, CGI-I score, mother satisfaction and psychosomatic problems. There were no significant differences in the effectiveness between the AHC and IR-MPH groups. The adverse events related to the therapy with IR-MPH, OROS-MPH or AHC were mild and the incidence rates of adverse events were not significantly different among the three groups.</p><p><b>CONCLUSIONS</b>The effectiveness of OROS-MPH for the treatment of ADHD is probably superior to IR-MPH, and the effectiveness between AHC and IR-MPH is similar. The three drugs demonstrate the safety and well tolerance.</p>