Dose-Dependent Effects of Ceruletide on Jejunal Motor Activity and on Experimentally Induced Pain in Healthy Humans
Ceruletide stimulates the contractile activity of the distal duodenum and the jejunum and accelerates small intestinal transit. Recently it was found that the peptide also exerts analgesic effects. This study investigated whether i.m. doses of 5, 10, and 20 μg ceruletide (Farmitalia Carlo Erba, Milan, Italy) would, in comparison with placebo, both stimulate jejunal motility and alleviate experimentally induced pain. Sixteen healthy men (age 20 – 32 yr) participated each in four experiments one week apart and received, in random double-blind fashion, all of the treatments. Jejunal pressures were recorded continuously by three perfused catheters with orifices spaced 3 cm apart and positioned 10 to 20 cm beyond the ligament of Treitz. The pressure recordings were analysed by computer. Chains of square wave constant current impulses of increasing intensity administered to the subjects’ earlobe and constant intensity, variable time radiant heat stimuli applied sequentially to six spots on the forearm were used to induce pain. Each experiment lasted 150 min, 30 before and 120 min after drug administration. Ceruletide dose-dependently increased phase II (P < 0.001) and decreased phase I type activity (P < 0.001) and the occurrence of activity fronts (Fig. 1). The number and amplitude of contractions as well as the area under the pressure curve (Fig. 2) increased significantly and dose-dependently (P < 0.001). Ceruletide also increased dose-dependently threshold (P < 0.001) and tolerance (P < 0.001; Fig. 3) to electrically induced pain and threshold to thermally induced pain (P < 0.05; Fig. 4). All effects lasted dose-dependently for 60 to more than 120 min. Only mild sedative and other side effects occurred; respiration, heart-rate, and blood pressure remained unaffected.