gonist in comparison with placebo. The visual analog scale demonstrated that 50 mg of L-365,260 significantly lowered anxiety scores after administration of CCK4. The authors believe that their study demonstrated that CCK-B receptors are "an important site of action of exogenous CCK-4 in humans"4, though it is not clear due to the lack of knowledge about CCK permeability of blood-brain barrier whether these receptors are the primary source of action. The study with another CCK-4 antagonist, CI-988, was conducted by the same group of researchers a year later ( Bradwejn et al., 1995).5 Unlike the experiment with L-365,260, this study included only healthy volunteers with no history of panic disorder. The participants were injected with either 50 g of CCK-4 or placebo. A higher dose of CCK-4 than in the L-365,260 experiment was chosen for the healthy subjects, and the antagonist was given orally 30 min before CCK-4 injection. The evaluation of CI-988 performances was judged with the help of the PSS scale employed in the previous studies and cardiovascular response monitoring. The results of the experiment showed that CI-988 had weaker anxiolytic properties than L-365,260. The number of symptoms was not significantly reduced, though a sum intensity of symptoms and panic attack rate decreased significantly. The subjective experience of anxiety/fear/apprehension was attenuated significantly in comparison with all other symptoms, and researchers ascribe this specific effect to a decrease in panic attack rate. The scientist view ability of CI-988 to reduce anxiety levels as an indicator of CCK-4 involvement in ethiology of panic attacks. They contribute moderate efficacy of this antagonist to its poor availability in the systemic circulation, rather than to unsuitability of healthy volunteers for CCK-B antagonists studies. In support, they refer to the corroborating L-365,260 studies with healthy subjects and CI-988 studies with PD...
