The effects of DEX are not limited to its interactions with alpha2-adrenergic receptors. Inhibitory effects on I(K(DR)) and I(Na) constitute one of the underlying mechanisms through which DEX and its structurally related compounds might affect neuronal activity in vivo.

No abstract

For sedated colonoscopy, propofol in combination with meperidine is better than propofol alone in improving patients' tolerance and recovery.

Abstract. Ranolazine, a piperazine derivative, is currently approved for the treatment of chronic angina. However, its ionic mechanisms in other types of cells remain unclear, although it is thought to be a selective blocker of late Na + current. This study was conducted to evaluate the possible effects of ranolazine on Na, and Ca 2+-activated K + current (I K(Ca) ) in pituitary tumor (GH 3 ) cells. Ranolazine depressed the transient and late components of I Na with different potencies. This drug exerted an inhibitory effect on I K(IR) with an IC 50 value of 0.92 μM, while it slightly inhibited I K(DR) and I K(Ca) . It shifted the steady-state activation curve of I K(IR) to more positive potentials with no change in the gating charge of the channel. Ranolazine (30 μM) also reduced the activity of large-conductance Ca 2+-activated K + channels in HEK293T cells expressing α-hSlo. Under current-clamp conditions, low concentrations (e.g., 1 μM) of ranolazine increased the firing of action potentials, while at high concentrations (≥10 μM), it diminished the firing discharge. The exposure to ranolazine also suppressed I Na and I K(IR) effectively in NG108-15 neuronal cells. Our study provides evidence that ranolazine could block multiple ion currents such as I Na and I K(IR) and suggests that these actions may contribute to some of the functional activities of neurons and endocrine or neuroendocrine cells in vivo.