Abstract

Aim:Metergoline is an ergot-derived psychoactive drug that acts as a ligand for serotonin and dopamine receptors. The aim of this study was to investigate the regulatory effects of metergoline on the neuronal Nav1.2 voltage-dependent Na⁺ channels in vitro.Methods:Xenopus oocytes were injected with cRNAs encoding rat brain Nav1.2 α and β1 subunits. Voltage-activated Na + currents were recorded using two-electrode voltage clamp technique. Drugs were applied though perfusion. Results: Both metergoline and lidocaine reversibly and concentration-dependently inhibited the peak of Na⁺ currents with IC 50 values of 3.6±4.2 and 916.9±98.8 μmol/L, respectively. Metergoline (3 μmol/L) caused a 6.8±1.2 mV depolarizing shift of the steady-state activation curve of the Na⁺ currents, and did not alter the inactivation curve. In contrast, lidocaine (3 μmol/L) caused a 12.7±1.2 mV hyperpolarizing shift of the inactivation curve of the Na⁺ currents without changing the steady-state activation curve. Both metergoline and lidocaine produced tonic and use-dependent inhibition on the peak of Na + currents.Conclusion:Metergoline exerts potent inhibition on the activity of neuronal Nav1.2 channels, which may contribute to its actions on the central nervous system. © 2014 CPS and SIMM.

Author keywords

Antidepressant; Ergot alkaloid; Lidocaine; Metergoline; Nav1.2; Xenopus oocyte

Indexed keywords

EMTREE drug terms: complementary RNA; lidocaine; metergoline; nav1.2 alpha subunit; nav1.2 beta1 subunit; sodium channel Nav1.2; unclassified drug

EMTREE medical terms: animal cell; article; brain function; concentration response; controlled study; drug potency; hyperpolarization; IC 50; in vitro study; nonhuman; oocyte; perfusion; protein expression; regulatory mechanism; sodium current; steady state; voltage clamp technique; Xenopus laevis

Chemicals and CAS Registry Numbers: lidocaine, 137-58-6, 24847-67-4, 56934-02-2, 73-78-9; metergoline, 17692-51-2

Manufacturers:Drug manufacturer: Tocris, United States.