LY544344 is a LY354740 prodrug that increases LY354740 bioavailability. This 8-week study was designed to evaluate the efficacy, safety, and tolerability of LY544344 in the treatment of GAD. Participants had a diagnoses of GAD, baseline Hospital Anxiety and Depression Scale anxiety subscale scores >= 10, and moderate illness severity. Patients were randomized to double-blind treatment with LY544344 16 mg b.i.d. (n = 28), LY544344 8mg b. i. d. (n 36), or placebo (n = 44). LY544344 16 mg b.i.d.treated patients showed significantly greater improvement from baseline in Hamilton Anxiety and Clinical Global Impression-Improvement scores, as well as response and remission rates compared with placebo-treated patients. LY544344

was well tolerated and there were no significant differences in the incidence of treatment-emergent adverse events among the three treatment groups. However, Tariquidar mw Cyclosporin A ic50 the trial was discontinued early based on findings of convulsions in preclinical studies. In conclusion, the findings of this study support the potential efficacy of mGlu2/3 receptor agonist agents in the treatment of GAD. Additional studies will be needed

to further assess the toxicological and clinical profile of LY354740/ LY544344.”
“TBZE-029 1-(2,6-difluorophenyl)-6-trifluoromethyl-1H,3H-thiazolo[3,4-albenzimidazole is a novel selective inhibitor of the replication of several enteroviruses. We show that TBZE-029 exerts its antiviral activity through inhibition of viral RNA replication, without affecting polyprotein processing. To identify the viral target of TBZE-029,

drug-resistant coxsackievirus B3 (CVB3) was selected. Genotyping of resistant clones led to the identification of three amino acid mutations in nonstructural protein 2C, clustered at amino acid positions 224, 227, and 229, immediately downstream of NTPase/helicase motif C. The mutations were reintroduced, either alone or combined, into an infectious full-length CVB3 clone. In particular the mutations at positions 227 and 229 proved essential for the altered sensitivity of CVB3 Akt inhibitor to TBZE-029. Resistant virus exhibited cross-resistance to the earlier-reported antienterovirus agents targeting 2C, namely, guanidine hydrochloride, HBB [2-(alpha-hydroxybenzyl)-benzimidazole], and MRL-1237 1-(4-fluorophenyl)-2-[(4-imino-1,4-dihydropyridin-1-yl)methyl]benzimidazole hydrochloride. The ATPase activity of 2C, however, remained unaltered in the presence of TBZE-029.”
“Phosphodiesterase-4 (PDE4), an enzyme that catalyzes the hydrolysis of cyclic AMP and plays a critical role in controlling its intracellular concentration, has been implicated in depression- and anxiety-like behaviors. However, the functions of the four PDE4 subfamilies (PDE4A, PDE4B, PDE4C, and PDE4D) remain largely unknown. In animal tests sensitive to anxiolytics, antidepressants, memory enhancers, or analgesics, we examined the behavioral phenotype of mice deficient in PDE4B (PDE4B-/-).