Erythrina mulungu alkaloids are potent inhibitors of neuronal nicotinic receptor currents in mammalian cells.

Crude extracts and three isolated alkaloids from Erythrina mulungu plants have shown anxiolytic effects in different animal models. We investigated whether these alkaloids could affect nicotinic acetylcholine receptors and if they are selective for different central nervous system (CNS) subtypes. Screening experiments were performed using a single concentration of the alkaloid co-applied with acetylcholine in whole cell patch-clamp recordings in three different cell models: (i) PC12 cells natively expressing α3* nicotinic acetylcholine receptors; (ii) cultured hippocampal neurons natively expressing α7* nicotinic acetylcholine receptors; and (iii) HEK 293 cells heterologoulsy expressing α4ß2 nicotinic acetylcholine receptors. For all three receptors, the percent inhibition of acetylcholine-activated currents by (+)-11á-hydroxyerysotrine was the lowest, whereas (+)-erythravine and (+)-11á-hydroxyerythravine inhibited the currents to a greater extent. For the latter two substances, we obtained concentration-response curves with a pre-application protocol for the α7* and α4ß2 nicotinic acetylcholine receptors. The IC50 obtained with (+)-erythravine and (+)-11á-hydroxyerythravine were 6 µM and 5 µM for the α7* receptors, and 13 nM and 4 nM for the α4ß2 receptors, respectively. Our data suggest that these Erythrina alkaloids may exert their behavioral effects through inhibition of CNS nicotinic acetylcholine receptors, particularly the α4ß2 subtype.

Effects of acute and chronic treatment with Hypericum perforatum L. (LI 160) on different anxiety-related responses in rats.

The study investigates the effects of acute and chronic oral treatment with Hypericum perforatum L. (HP LI 160, 62.5-500 mg/kg) in rats submitted to different anxiety models: the elevated T-maze (for inhibitory avoidance and escape measurements), the light/dark transition, and the cat odor test. These models were selected for their presumed capacity of evidencing specific subtypes of anxiety disorders as recognized in clinical practice. The results showed that acute HP (125 mg/kg) impaired elevated T-maze inhibitory avoidance, an anxiolytic effect, without altering escape performance. Chronic HP (250 mg/kg) enhanced avoidance latencies only in animals that were preexposed to the open arms of the maze. Preexposure shortens escape latency, improving it as an escape index. Differently from the reference drug imipramine (IMP, 15 mg/kg), chronic HP did not impair escape from the open arms of the maze. On the other hand, similarly to IMP, the extract increased the number of transitions between the two compartments in the light/dark transition model. Treatment regimens with HP and IMP did not alter behavioral responses of rats to a cloth impregnated with cat odor. These observations suggest that HP LI 160 exerts anxiolytic-like effects in a specific subset of defensive behaviors, particularly those related to generalized anxiety.