Dantrolene-Induced Inhibition of Skeletal L-Type Ca(2+) Current Requires RyR1 Expression.

Dantrolene-Induced Inhibition of Skeletal L-Type Ca(2+) Current Requires RyR1 Expression.

Biomed Res Int. 2013; 2013: 390493
Bannister RA

Malignant hyperthermia (MH) is a pharmacogenetic disorder most often linked to mutations in the type 1 ryanodine receptor (RyR1) or the skeletal L-type Ca(2+) channel (CaV1.1). The only effective treatment for an MH crisis is administration of the hydantoin derivative Dantrolene. In addition to reducing voltage induced Ca(2+) release from the sarcoplasmic reticulum, Dantrolene was recently found to inhibit L-type currents in developing myotubes by shifting the voltage-dependence of CaV1.1 channel activation to more depolarizing potentials. Thus, the purpose of this study was to obtain information regarding the mechanism of Dantrolene-induced inhibition of CaV1.1. A mechanism involving a general depression of plasma membrane excitability was excluded because the biophysical properties of skeletal muscle Na(+) current in normal mouse myotubes were largely unaffected by exposure to Dantrolene. However, a role for RyR1 was evident as Dantrolene failed to alter the amplitude, voltage dependence and inactivation kinetics of L-type currents recorded from dyspedic (RyR1 null) myotubes. Taken together, these results suggest that the mechanism of Dantrolene-induced inhibition of the skeletal muscle L-type Ca(2+) current is related to altered communication between CaV1.1 and RyR1. HubMed – depression


Contemporary concepts in the pharmacotherapy of depression in older people.

Can Pharm J (Ott). 2012 May; 145(3): 128-135.e2
Rojas-Fernandez C, Mikhail M

Late-life depression is common in older people. Its incidence increases significantly after age 70 to 85, as well as among those living in long-term care facilities. Depression contributes to excess morbidity and complicates management of comorbid conditions in older people. Diagnosis and management of depression often present clinicians with a challenge. Indeed, symptoms of depression in older people may not always be the same as those associated with depression in younger people. Additionally, age-related changes in pharmacokinetics and pharmacodynamics also impact selection, dosing, and monitoring of psychopharmacologic regimens. Optimizing management of depression and providing sound advice to older patients with depression requires knowledge and understanding of many clinical factors. The purpose of this review is to highlight salient issues in late-life depression, with a focus on the pharmacotherapy of depression. HubMed – depression


Use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy and disorganized infant-mother attachment.

J Reprod Infant Psychol. 2012 Jul 1; 30(3): 261-277
Troutman BR, Momany AM

Examine the quality of infant-mother attachment in a prospective case series of infants whose mothers took selective serotonin reuptake inhibitors (SSRIs) during pregnancy.SSRIs are prescribed to 2 to 6% of pregnant women (National Collaborating Centre for Mental Health, 2007; Stewart, 2011). Recent articles on the use of SSRIs during pregnancy note the increased risk for problematic infant-mother relationships among mothers with untreated postpartum depression (Gentile, 2011; Stewart, 2011). However, little is known about the quality of infant-mother relationships among mothers who took SSRIs during pregnancy.Five mothers who took SSRIs during pregnancy were recruited from a community study of infant development. Mothers completed ratings of postpartum depression symptoms (Beck Depression Inventory) 4 to 6 times between 1 month and 1 year following the infant’s birth. At 1 year postpartum, quality of infant-mother attachment was assessed using the strange situation procedure.Four of the 5 infant-mother dyads (80%) were classified as disorganized, a rate considerably higher than in postpartum depression samples.These results are used to raise questions about the clinical implications of research on in utero exposure to SSRIs, perinatal depression, and disorganized attachment. Specifically, this case series raises questions about using research on the link between postpartum depression and infant-mother attachment as a rationale for the use of SSRIs during pregnancy. Current research indicates use of SSRIs during pregnancy may: 1) increase risk for disorganized attachment, 2) decrease risk for disorganized attachment, or 3) have no effect on disorganized attachment. HubMed – depression



NeuroStar TMS Therapy on The Daily Buzz morning show Sept 12, 2012. – Nearly 20 million Americans suffer from depression. Today we’re focusing on a breakthrough treatment that uses magnetic stimulation. TMS, transcranial magnet…