Calcium-Dependent Interplay of Lithium and Tricyclic Antidepressants, Amitriptyline and Desipramine, on <i>N</i>-methyl-D-aspartate Receptors

The facilitated activity of N-methyl-D-aspartate receptors (NMDARs) in the central and peripheral nervous systems promotes neuropathic pain. Amitriptyline (ATL) and desipramine (DES) are tricyclic antidepressants (TCAs) whose anti-NMDAR properties contribute to their analgetic effects. At therapeutic concentrations +, which suppresses the sodium–calcium exchanger (NCX) and enhances NMDAR CDD, also exhibits analgesia. Here, the effects of different [Li+]s on TCA inhibition of currents through native NMDARs in rat cortical neurons recorded by the patch-clamp technique were investigated. We demonstrated that the therapeutic [Li+]s of 0.5–1 mM cause an increase in ATL and DES IC50s of ~10 folds and ~4 folds, respectively, for the Ca2+-dependent NMDAR inhibition. The Ca2+-resistant component of NMDAR inhibition by TCAs, the open-channel block, was not affected by Li+. In agreement, clomipramine providing exclusively the NMDAR open-channel block is not sensitive to Li+. This Ca2+-dependent interplay between Li+, ATL, and DES could be determined by their competition for the same molecular target. Thus, submillimolar [Li+]s may weaken ATL and DES effects during combined therapy. The data suggest that Li+, ATL, and DES can enhance NMDAR CDD through NCX inhibition. This ability implies a drug–drug or ion–drug interaction when these medicines are used together therapeutically

Loss of signal during intraoperative neuromonitoring of laryngeal nerves as a predictor of postoperative larynx paresis: Analysis of 1065 consequetive thyroid and parathyroid operations. Surgeons' algorythm (tactics)

During thyroid and parathyroid operations performed with laryngeal nerves neuromonitoring, a segmental or global loss of signal may occur. The most frequent cause of loss of signal – is tension of thyroid gland tissue and at the same time tension of the laryngeal nerves. There is no consensus if this complication arises regarding surgeon’s actions. Aim. Evaluation of predictive value of loss of signal during IONM regarding larynx paresis in postoperative period, and algorithm suggestion in case of loss of signal develops. Materials and methods. 1065 patients were operated on thyroid and parathyroid glands with neuromonitoring of laryngeal nerves. Neuromonitore C2 (Inomed, Emmendingen, Germany) was used. We evaluated frequency of loss of signal, described types of loss of signal, showed sensitivity and specificity of loss of signal and development of postoperative larynx paresis. Results. Loss of signal developed in 32 (1,9%) patients. More frequently loss of signal was detected at left side (p=0,01, χ2 = 4,2 OR=2,9). Sensitivity (Se)  of loss of signal and postoperative larynx paresis development reached 59,2%, specificity – 99,7% (Sp), positive predicitive value (PPV) – 91,4%, negative predictive value (NPV) – 97,8%. There are no statistically reliable differences in recovery periods of larynx function depending on type of loss of signal (segmental or global) (p=0,5). Conclusions. In most cases loss of electromyographical signal indicates injury of laryngeal nerves during operation on thyroid and parathyroid glands. When there is loss of signal in case of bilateral thyroid gland disease it is reasonable to make a decision to stop operation to prevent development of bilateral larynx paresis