CYP2D6 predicted metabolizer status and safety in adult patients with attention-deficit hyperactivity disorder participating in a large placebo-controlled atomoxetine maintenance of response clinical trial.

Atomoxetine, which is indicated for treatment of attention-deficit hyperactivity disorder (ADHD), is predominantly metabolized by genetically polymorphic cytochrome P450 2D6 (CYP2D6). Based on identified CYP2D6 genotypes, individuals can be categorized into 4 phenotypic metabolizer groups as ultrarapid, extensive, intermediate, and poor. Previous studies have focused on observed differences between poor and extensive metabolizers, but it is not well understood whether the safety profile of intermediate metabolizers differs from that of ultrarapid and extensive metabolizers.

Gain and loss of function of P2X7 receptors: mechanisms, pharmacology and relevance to diabetic neuropathic pain.

Background: Genetic causes of exaggerated or reduced pain sensitivity in humans are well known. Recently, single nucleotide polymorphisms (SNPs) in the gene P2RX7, coding for the ATP-gated ion channel P2X7, have been described that cause gain-of-function (GOF) and loss-of-function (LOF), respectively of this channel. Importantly, P2RX7 SNPs have been associated with more or less severe pain scores in patient suffering of post-mastectomy pain and osteoarthritis.

A phase 2, placebo-controlled study of the opioid receptor antagonist LY2196044 for the treatment of alcohol dependence.

Background: Endogenous opioid-mediated reward pathways may play a role in the development and maintenance of alcohol dependence. This study tested whether LY2196044, an opioid receptor antagonist, in combination with medical management would reduce drinking in alcohol-dependent patients.

Methods: This was a multicenter, outpatient, randomized, double-blind, parallel, and placebo-controlled trial with a 16-week treatment period.

Association of candidate gene polymorphisms with diastolic blood pressure change in patients treated with duloxetine.

Single nucleotide polymorphisms in six genes were investigated for an association between diastolic blood pressure change and duloxetine treatment. Nominally significant within-gene association was found with SLC6A2 rs4436775 and rs4564560 and HTR2A rs6313, but after adjusting for multiple comparisons, these associations were no longer significant.

Pharmacogenomic associations with weight gain in olanzapine treatment of patients without schizophrenia.

Objective: Pharmacogenomic analyses of weight gain during treatment with second-generation antipsychotics have resulted in a number of associations with variants in ankyrin repeat and kinase domain containing 1 (ANKK1)/dopamine D2 receptor (DRD2) and serotonin 2C receptor (HTR2C) genes. These studies primarily assessed subjects with schizophrenia who had prior antipsychotic exposure that may have influenced the amount of weight gained from subsequent therapies. We assessed the relationships between single-nucleotide polymorphisms (SNPs) in these genes with weight gain during treatment with olanzapine in a predominantly antipsychotic-naive population.