Synergistic anticholinergic and antiserotonergic effects in humans

Animal research suggests an important interactive role for ascending cholinergic and serotonergic systems in modulation of cerebral function. Employing a randomized, double-blind, crossover design, 11 healthy young adults were tested in each of four conditions: (1) placebo, (2) fenfluramine (a serotonin depleting agent), (3) scopolamine (a muscarinic antagonist), and (4) fenfluramine and scopolamine. P3 latency was slowed by the dual drug treatment to an extent greater than the sum of individual drug effects. EEG mean frequency was decreased by behavioral activation, and this decrease was reversed by the combined drug treatment but not by single drugs. In contrast, verbal memory, EEG alpha power, and P3 amplitude were significantly affected only by scopolamine. No drug effects were found for the N1 and P2 potentials. The results provide the first demonstration of combined anticholinergic and antiserotonergic effects in humans, and offer partial support to the concept of an interactive role of cholinergic and serotonergic systems in cerebral mechanisms.