Anxiolytic effects of low-dose clomipramine in highly anxious healthy volunteers assessed by frontal midline theta activity.

1. The appearance of Fm theta, the distinct EEG theta rhythm in the frontal midline area during performance of a mental task, reflects relief from anxiety in humans. 2. In the present study, the anxiolytic effects of low-dose clomipramine were examined by monitoring the Fm theta amount, the STAI scores and the plasma 5-HIAA concentration in 24 male university students with (Fm theta group, n = 12) and without (non-Fm theta group, n = 12) Fm theta. 3. Subjects were given placebo, 10 mg and 30 mg clomipramine in a double-blind crossover design. Blood samples were obtained, STAI scores were determined, and EEGs were recorded before and during the performance of an arithmetic addition task. The test was repeated twice: before and 3 hrs after drug administration. 4. In the non-Fm theta group, 10 mg clomipramine decreased the 5-HIAA concentration and state anxiety scores but increased the Fm theta amount, while 30 mg clomipramine slightly increased only the Fm theta amount. However, there were no differences in these items before and after clomipramine administration in the Fm theta group. 5. These results suggest that low doses of clomipramine such as 10 mg may exert anxiolytic effects during the acute phase of treatment in highly anxious humans.

A useful tool for predicting the clinical effects of hypnotics in humans: averaged photopalpebral reflex.

The averaged photopalpebral reflex (PPR) is an index which objectively assesses the arousal level of humans. The dose-response curve of flunitrazepam, a benzodiazepine derivative, was investigated by using PPR in the present study. Ten healthy male university students were given flunitrazepam 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and placebo in a double-blind, crossover design. PPR and subjective assessment were recorded before and after drug administration. P1 and P2 latencies of PPR were prolonged by flunitrazepam 0.5 mg, 1.0 mg and 1.5 mg in a dose-dependent manner. The prolongation of latencies by flunitrazepam 2.0 mg was weaker than that by 1.5 mg, but was more potent than that by 1.0 mg. In self-assessments, sleepiness, muscle weakness and vagueness of thought were observed after drug ingestion. Sleepiness was correlated with the prolongation of the PPR latencies. These results suggest that PPR could be a useful tool for psychopharmacological investigations in normal humans, that flunitrazepam might be a clinically potent hypnotic drug, and that its peak effect occurs 2-3 h after administration.

Characteristics of yawning behavior induced by apomorphine, physostigmine and pilocarpine.

Apomorphine, a dopamine receptor agonist, physostigmine, an anticholinesterase agent and pilocarpine, a cholinergic receptor agonist, produced yawning in rats, with the most effective doses being 0.25 mg/kg, 0.2 mg/kg and 4 mg/kg, respectively. The yawning induced by these drugs is characterized by differences in direction of head moving, tongue protruding and duration of the yawn. The apomorphine-induced yawn was characterized by a slow and wide opening of the mouth with the head moving mainly downward and with a marked protrusion of the tongue. The apomorphine-induced yawn was 3.6 sec in duration. Physostigmine elicited a similar yawn to that seen with apomorphine, except for moving of the head in the upward direction. The pilocarpine-induced yawn was characterized by the head moving forward with a high frequency but without tongue protrusion and lasted 1.8 sec. The frequency of physiological yawning was low, but the behavioral posture was almost similar to that of physostigmine-induced yawning. The characteristics of yawns induced by these agents were unchanged at all doses of the drugs. Different doses altered the frequency of yawning. After pretreatment with mecamylamine, the apomorphine- and physostigmine-induced tongue protruding was inhibited and the duration of the yawning induced by the both drugs was shortened. The results suggest that the behavioral features of yawning induced by apomorphine, physostigmine and pilocarpine differ from one another, and that physiological yawning as well as physostigmine-induced yawning may be mediated by endogenous acetylcholine which stimulates both muscarinic and nicotinic receptors.

Appearance of frontal midline theta rhythm and personality traits.

The distinct theta rhythm in the frontal midline area during a performance of mental tasks has been called Fm theta. However, Fm theta shows individual differences in its appearance. The relationship between the appearance of Fm theta and the subject personality was investigated in the present study. Forty male university students performed an arithmetic addition test for 5 min daily during three consecutive days and their EEGs were recorded during the test. They also completed the Maudsley Personality Inventory (MPI) and the Taylor Manifest Anxiety Scale (MAS) after the EEG recording on the last day. The subjects who obtained low scores on the anxiety scale of MAS, high scores on the extraversion scale of MPI and low scores on the neuroticism scale of MPI showed larger amounts of Fm theta. On the other hand, those subjects who showed high scores on the anxiety scale, low scores on the extraversion scale and high scores on the neuroticism scale showed smaller amounts of Fm theta or none. These results suggest that the appearance of Fm theta is closely related to the subject personality traits.