No abstract

Despite the relatively safe and benign adverse effect profile of the selective serotonin-reuptake inhibitors such as fluvoxamine, clinicians should be cautious about seizures as an adverse effect, especially when the patient has even a remote history of seizure or head trauma.

Background and purpose:Indacaterol is a novel b2-adrenoceptor agonist in development for the treatment of chronic obstructive pulmonary disease. The aim of this study was to investigate the comparative pharmacology of indacaterol in recombinant cells expressing the common polymorphic variants of the human b2-adrenoceptor and in human primary airway smooth muscle (ASM) cells. Experimental approach: Chinese hamster ovarian-K1 cell lines expressing high and low levels of the common human b2-adrenoceptor variants were generated [Gly16-Glu27-Val34-Thr164(GEVT), RQVT, GQVT] and also the rare GQVI variant. Human primary ASM cells were isolated from explants of trachealis muscle. Adenosine-3′,5′-cyclic-monophosphate production was used as an outcome measure. Key results: In both the low-and high-expression recombinant GEVT 'wild type' cell lines indacaterol is a high-efficacy agonist. Salmeterol and formoterol were identified as low-and high-efficacy agonists, respectively, and showed similar potencies to indacaterol irrespective of the b2-adrenoceptor genotype. The I164 variant cell line was associated with a reduced capacity to generate adenosine-3′,5′-cyclic-monophosphate in response to b2-adrenoceptor agonist. In the human primary ASM cells indacaterol gave a maximal response intermediate between that of salmeterol and formoterol. Conclusions and implications:These data demonstrate that indacaterol is a high-efficacy agonist in recombinant cell systems but acts with lower efficacy in human primary ASM cells. No marked genotype-dependent effects were observed for common variants; however, changes in I164 receptor activity were identified, which were dependent on the level of expression of b2-adrenoceptors.

Head injury of any severity can result in acute and chronic neuropsychiatric symptoms. After head injury, aggressive behaviors can be disabling to victims and stressful to their families. When aggression is compounded by dementia, treatment can be more difficult. Psychotropic agents can attenuate aggressive behaviors associated with mental disorders. Three patients with dementia and chronic aggression after head injury responded favorably to selective serotonin reuptake inhibitors.