It has been hypothesized that, in the absence of acute or chronic pain, a tonically active system exists involving opioid peptides, which ensures a certain level of pain insensitivity. Although various studies have failed to support this concept, it has been reported that in conditions of both experimentally induced and clinical pain, high doses of the opioid antagonist naloxone induced a state of hyperalgesia and thus seemed to set off this hypothetical system. Lower doses were, however, without effect or even acted as analgesics. This study investigated the effect of 5 and 20 mg naloxone i.v., compared to placebo, on the perception of pain in healthy humans. Pain was induced by two methods, using electrical and thermal stimulation of the skin, which have previously been shown to be sensitive to the effects of opioid as well as of non-steroidal anti-inflammatory analgesics. Each of 12 males and 12 females participated in 3 experimental sessions, in which the treatments were administered double-blind according to a Latin square design. Threshold and tolerance to electrically induced pain and threshold to thermally induced pain were measured at 30 min intervals for 90 min before and 90 min after drug administration. Electrical stimuli were square wave constant current impulses of linearly increasing intensity; thermal stimuli were of constant intensity and variable duration. Threshold and tolerance to electrically induced pain were not altered by either dose of naloxone, whereas the threshold to thermally induced pain was significantly higher after both 5 and 20 mg naloxone than after placebo, the effects of the two naloxone doses not differing from each other.(ABSTRACT TRUNCATED AT 250 WORDS)

This crossover, double-blind study investigated the effects of single oral doses of the prodrug loperamide oxide, which is reduced gradually to loperamide in the intestine, and loperamide on jejunal motor activity in 12 fasting healthy men. Five minutes after a phase III of the migrating motor complex (MMC), 2 mg loperamide oxide, 4 mg loperamide oxide, 4 mg loperamide, or placebo were administered. Thereafter, motor activity 10-30 cm abroad the ligament of Treitz was recorded with five catheter orifices at 3-cm intervals over 4 hr. Number of contractions and area under curve increased significantly with 4 mg loperamide and 4 mg loperamide oxide, the increases with loperamide oxide occurring more gradually. Placebo and 2 mg loperamide oxide had no discernible effects. With both 4 mg loperamide and 4 mg loperamide oxide, phase I of the MMC was slightly prolonged and phase II and the time from drug administration to the onset of the first phase III slightly shortened. The percentage of aborally propagated contractions in phase II increased with all active treatments, whereas the occurrence of phases III was not altered.

The evaluation of agents potentially accelerating gastric emptying in gastric stasis syndromes is time-consuming. Since a previous study showed that emptying is slowed after antecedent fat ingestion and intravenous cisapride abolishes this effect, we investigated whether emptying delayed by fat incorporated into a meal is reversed by cisapride and thus could serve as a model for such evaluations. Twelve healthy males received, under double-blind conditions, 30 mg cisapride rectally or placebo, and 3 hr thereafter a semisolid meal of low (9.2 g) or high (37.9 g) fat content. The sequence of combinations placebo/low-fat meal, placebo/high-fat meal, and cisapride/high-fat meal was randomized. Gastric emptying and antral motility were recorded scintigraphically. After placebo/high-fat, emptying was significantly slower (P less than 0.05) than after placebo/low-fat. After cisapride/high-fat, emptying was significantly faster (P less than 0.01) than after placebo/high-fat and similar to that after placebo/low-fat. Antral motility was little affected. The slow emptying of a high-fat meal thus seems a suitable model for the evaluation of prokinetic drug effects.

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1. The selective 5‐HT3 receptor antagonist, ICS 205‐930 (Sandoz), has been reported to have potent effects on gastric smooth muscle in vivo and to enhance gastric emptying in animals and in man. 2. This study investigated the effects of ICS 205‐930 on fat‐delayed gastric emptying of a semisolid meal and antral motor activity in humans. 3. Twelve healthy men participated in each of three studies in which 10 or 20 mg of ICS 205‐930 or placebo were infused i.v. in a random double‐blind fashion. Gastric emptying and antral motor activity were studied scintigraphically. 4. Gastric emptying was not altered after 10 mg but slower after 20 mg of ICS 205‐930 than after placebo. Emptying after 20 mg of ICS 205‐930 was significantly slower than after 10 mg of ICS 205‐ 930. 5. Antral contraction amplitude was slightly lower after 20 mg of ICS 205‐930 than after placebo, whereas the effects of 10 mg ICS 205‐ 930 did not differ from those of placebo. 6. The results suggest that the investigated doses of ICS 205‐930 have only slight effects on gastric motor activity of healthy young men, with 20 mg reducing the rate of emptying.