Inhibition of P‐glycoprotein enhances transport of imipramine across the blood–brain barrier: microdialysis studies in conscious freely moving rats
CONCLUSIONS AND IMPLICATIONSThe present study demonstrated that P‐gp inhibition enhanced the intracerebral concentration of imipramine , thus supporting the hypothesis that P‐gp activity restricts brain levels of certain antidepressants, including imipramine. These findings may help to explain reports of a beneficial response to adjunctive therapy with verapamil in TRD. (Source: British Journal of Pharmacology)

A Common β1-Adrenergic Receptor Polymorphism Predicts Favorable Response to Rate-Control Therapy in Atrial Fibrillation
Conclusions: We have identified a common β1-AR polymorphism, G389R, that is associated with adequate response to rate-control therapy in AF patients. Gly389 is a loss-of-function variant; consequently, for the same adrenergic stimulation, it produces reduced levels of adenyl cyclase, and hence, attenuates the β-adrenergic cascade. Mechanistically, the effect of rate-control drugs will be synergistic with that of the Gly389 variant, which could possibly explain our findings. These findings represent a step forward in the development of a long-term strategy of selecting treatment options in AF based on genotype. (Source: Journal of the American College of Cardiology)