The ability of PK 8165, a quinoline derivative, to reduce responses to a stressful situation in a double-blind study in man.

A double-blind and cross-over study was carried out in order to explore the effects of PK 8165 (a quinoline derivative) on the heart rate, respiratory rate and motor reflex responses produced by an experimental model of stress in 8 healthy volunteers. The stress was induced by repetitive sequences of anticipation of pain (stressful stimulus: S) spaced by resting periods (R). In a control session, the cumulative effects of S resulted, in all subjects, in a progressive increase in heart and respiratory rates; 5 subjects showed a cumulative facilitation in the H reflex (motor reflex response) while the 3 others exhibited a cumulative depression in this motor parameter as a function of repetition of S during the session. The three doses (50, 100, 150 mg) of PK 8165 produced a very significant dose-dependent reduction in these responses during both stressful periods and resting sequences. Furthermore, the baseline values of respiratory and especially heart rate were also significantly reduced in a dose-dependent fashion by PK 8165. In contrast, the treatment with placebo did not significantly modify these parameters, compared to control values. The functional implications of these data are discussed in terms of stress-induced activation of some CNS structures and of the possible mechanisms of the "anti-stress" effect of PK 8165.