Open-label study comparing the efficacy and tolerability of aripiprazole and haloperidol in the treatment of pediatric tic disorders

Due to its unique pharmacodynamic properties of dopamine partial agonist activity, and its association with few and mild side effects, aripiprazole is a candidate atypical antipsychotic for patients with tic disorders. This open-label study compared the efficacy and tolerability of aripiprazole with haloperidol, a typical antipsychotic widely used to treat patients with tic disorders. Forty-eight children and adolescents with tic disorders were recruited from the outpatient clinic at South Korea and treated with aripiprazole (initial dose, 5.0 mg/d; maximum dose 20 mg/d) or haloperidol (initial dose, 0.75 mg/d; maximum dose, 4.5 mg/d) for 8 weeks. Treatment efficacy was measured using the yale global tic severity scale (YGTSS), and tolerability was measured using the extrapyramidal symptom rating scale (ESRS) and an adverse effects checklist. Total tic scores as measured by the YGTSS decreased over time in both groups (p < 0.001) without any significant differences between groups. ESRS scores were significantly higher in the haloperidol group during the 4 weeks after commencement of medication (p < 0.05). These results indicate that aripiprazole may be a promising drug in the treatment of children and adolescents with tic disorders. Further controlled studies are needed to determine the efficacy and tolerability of aripiprazole in these patients

Prostaglandin- and theophylline-induced Cl secretion in rat distal colon is inhibited by microtubule inhibitors

The aim of the present study was to examine the possible role of microtubules in chloride secretion by distal rat colon stimulated by prostaglandin (PGE 2 ) and theophylline. Distal colonic tissue from male rats was mounted in Ussing chambers, and short-circuit current (I sc ) was measured to assess chloride secretion. Three microtubule inhibitors, colchicine, nocodazole, and taxol, all inhibited the stimulated I sc and reduced the 60-min integrated secretory response to PGE 2 and theophylline (▪I sc dt) by 39–52%, whereas the inactive colchicine analog lumicolchicine did not. Atropine and tetrodotoxin had no effect on stimulated chloride secretion. To confirm the source of I sc , unidirectional 22 Na + and 36 Cl − fluxes were measured in tissues exposed to lumicolchicine (control) or colchicine. Control tissues absorbed both chloride [5.0 (1.1–8.6) (median and 95% confidence interval) μeq/cm 2 /hr] and sodium [2.8 (0.9–7.2) μeq/cm 2 /hr], and this net absorption was reduced by 96% and 79%, respectively, by treatment with PGE 2 and theophylline due to an increase in serosal-to-mucosal chloride and sodium movement. Colchicine-treated tissues exhibited similar net basal chloride and sodium absorption that was reduced by 71% and 75%, respectively, by treatment with PGE 2 and theophylline. Thus the PGE 2 - and theophylline-induced increase in chloride secretion was significantly reduced by colchicine ( P <0.05 by Wilcoxon rank-sum test), whereas colchicine had no effect on PGE 2 - and theophylline-induced changes in sodium fluxes. Furthermore, the colchinine-related changes in stimulated chloride secretion were numerically similar to colchicine-related changes in stimulated I sc . These findings indicate that microtubules are required for normal PGE 2 - and theophylline-induced chloride secretion in distal rat colon and suggest that induced chloride secretion may involve vesicular insertion of ion transporters into the plasma membrane or other microtubule-dependent regulatory processes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44414/1/10620_2005_Article_BF01299864.pd