Ceruletide increases threshold and tolerance to experimentally induced pain in healthy man

Schmierer³

et al. 1984

Gut

Ceruletide (INN proposed by the WHO) or, as it was named formerly, caerulein is a decapeptide of the amino acid sequence Pyr-Gln-Asp-Tyr(SO3H)-Thr-Gly-Trp-Met-Asp-Phe-NH2 and is structurally related to the cholecystokinin (CCK) -gastrin family. It was isolated from the skin of the Australian hylid frog Hyla caerulea by the group of Erspamer' and synthesised subsequently.2 The peptide has been reported to stimulate myoelectrical spiking as well as the contractile activity of the distal duodenum and the jejunum in man3 4 and, in the rat,5 to increase the tone of all segments of the small intestine except of the duodenum, and to reduce the transit time strikingly not only in healthy subjects but also in patients suffering from postoperative intestinal paralysis.6'l These actions of ceruletide parallel those of its mammalian counterpart cholecystokinin which has been shown to increase dose relatedly the motor activity of the jejunum 11-13 and to increase jejunal but not duodenal and ileal spike activity. 14 It has been discovered recently that these peptides not only have potent effects on the gastrointestinal tract but also are endowed with analgesic properties: in mice ceruletide and cholecystokinin 5, 10, and 20 utg intramuscularly would exert both stimulating effects on the motor activity of the upper jejunum and analgesic effects on experimentally induced pain in healthy human subjects. Methods SUBJECTSSixteen healthy men ranging in age from 20 to 32 years (mean 25-4 years) were studied. Only subjects not taking drugs at the time of the experiment, having regular bowel movements, and without any history of gastrointestinal disease or previous abdominal surgery were included. They were given a short explanation of the purpose of the research and a description of the procedures to be followed. They were further given a description of any reasonably foreseeable risks or discomforts. Written

Section: Discussionsupporting

confidence: 54%

mentioning

confidence: 99%

Ceruletide increases dose dependently both jejunal motor activity and threshold and tolerance to experimentally induced pain in healthy man.

Stacher¹,

Schmierer³

et al. 1984

Gut

“…Using the same methods, a methionine-enkephalin analogue (Stacher et al, 1979b), the opioid agonist/antagonist drugs meptazinol and pentazocine (Stacher et al, 1983), as well as ceruletide, a decapeptide closely related to cholecystokinin (Stacher et al, 1982b(Stacher et al, , 1984, could be shown to produce significantly more analgesia than placebo. For the detection of analgesic effects of nonsteroidal anti-inflammatory drugs, however, experimental pain models seemed much less suited.…”

Section: Introductionmentioning

confidence: 99%

Experimental pain induced by electrical and thermal stimulation of the skin in healthy man: sensitivity to 75 and 150 mg diclofenac sodium in comparison with 60 mg codeine and placebo.

Stacher¹,

Schneider³

et al. 1986

Brit J Clinical Pharma

Experimental pain induced by electrical and thermal stimulation of the skin in healthy man: sensitivity to 75 2 Experimental pain models have been shown to discriminate reliably between the effects of opioid analgesics and placebo but their sensitivity to nonsteroidal antiinflammatory agents is disputed. 3 This study investigated whether it would be possible by using electrically and thermally induced cutaneous pain to discriminate reliably the effects of single oral doses of 75 and 150 mg diclofenac sodium on the one hand and 60 mg codeine on the other from those of placebo. 4 Forty-eight healthy subjects participated each in four experiments in which they received, in random double-blind fashion, each of the treatments. Every experiment comprised eight series of measurements, two before and six after drug administration, carried out at 30 min intervals. 5 Diclofenac sodium produced significant dose-related increases of threshold and tolerance to electrically and threshold to thermally induced pain. 6 Codeine 60 mg was significantly superior to placebo in all pain measures. Its analgesic effects were stronger than those of diclofenac 75 mg but weaker than those of diclofenac 150mg. 7 Neither 150 mg nor 75 mg diclofenac caused more side effects than placebo, whereas codeine 60 mg elicited a high frequency of side effects. No severe adverse effects occurred after any one treatment. 8 The results suggest that both electrically and thermally induced cutaneous pain are well suited to evaluate analgesic effects not only of opioids but also of nonsteroidal antiinflammatory drugs.

“…Electrical stimulation Chains of square wave constant current impulses of 1 millisecond (ms) duration and a pulse frequency of 30 per second (s) were used to induce pain (Lahoda et al, 1977;Stacher et al, 1979Stacher et al, , 1982aStacher et al, , 1982b. The stimuli were administered by means of a pair of silver ball electrodes attached to the earlobule of the subjects' non-dominant side.…”

Section: Assessment Ofanalgesic Efficacymentioning

confidence: 99%

“…Thermal stimulation Radiant heat of a constant intensity was used to induce pain (Stacher et al, 1982a(Stacher et al, , 1982b. On the volar surface of the subjects' dominant forearm, six spots were marked and numbered from one to six.…”

Section: Assessment Ofanalgesic Efficacymentioning

confidence: 99%

Effects of graded oral doses of meptazinol and pentazocine in comparison with placebo on experimentally induced pain in healthy humans.

Stacher¹,

Winklehner³

et al. 1983

Brit J Clinical Pharma

Self Cite

The opioid agonist/antagonist meptazinol has proven to exert significant analgesia in a series of painful conditions. This study investigated the effects of single oral doses of meptazinol 100, 200, and 400 mg in comparison with pentazocine 50 and 100 mg and with placebo on experimentally induced pain. In addition, the side effect profiles were assessed. Twenty-four healthy subjects participated each in six experiments in which they received, in random double-blind fashion, each of the treatments. Every experiment comprised 10 series of measurements, two before and eight after drug administration, carried out at 30 min intervals. Meptazinol produced significant dose-related increases of threshold and tolerance to electrically and thermally induced pain. Meptazinol 400 mg was significantly superior to placebo in all pain measures and proved as effective as pentazocine 50 and 100 mg, which yielded about equal effects. Meptazinol 200 mg was significantly weaker than pentazocine 50 mg and differed significantly from placebo only in its effects on pain tolerance. Meptazinol did not cause any severe side effects or systematic alterations of respiration, blood pressure, heart rate and central nervous functions. Pentazocine caused a higher number and more severe side effects, one subject reporting severe dysphoria after pentazocine 100 mg. The results give further evidence that meptazinol is well suited to replace other opioid analgesics compromised by a high incidence of adverse effects.