Effect of the cholecystokinin-B receptor antagonist L-365,260 on lactate-induced panic attacks in panic disorder patients

Abstract

Panic attacks are characterized by a rapid crescendo of fear or apprehension associated with the endorsement of physical symptoms. In panic disorder (PD) patients these panic attacks occur usually spontaneously (American Psychiatric Association 1989). Panic attacks can also be provoked by a number of pharmacologic agents (Westenberg and den Boer 1994). Among the different panic-provoking substances, one of the most widely studied is sodium lactate (Liebowitz et al 1984; den Boer and Westenberg 1989). Although the exact mechanism by which sodium lactate induces panic remains unclear, it appears to be a valid model for panic attacks, and clinically effective antipanic agents have been found to be able to antagonize sodium-lactateinduced panic attacks (Rifkin et al 1981; Cowley et al 1991; Coplan et al 1992). An intriguing new development is the discovery that cholecystokinin-B (CCK-B) receptor agonists possess panic-inducing properties. Panic attacks elicited by CCK-B receptor agonists like CCK-4 and pentagastrin have been found to be similar to naturally occurring panic attacks (van Megen et al 1994). Recently, we have investigated the effect of the CCK-B receptor antagonist L-365,260 on CCK-4-induced panic attacks (Bradwejn et al 1994). L-365,260 was able to block CCK-4-induced panic attacks in a dose-dependent fashion. This raises the question whether this effect of L-365,260 can be