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Jeannemarie Lecomte - One of the best experts on this subject based on the ideXlab platform.

  • Double-Blind Study of Effects of Enkephalinase Inhibitor on Adverse Reactions to Myelography
    2016
    Co-Authors: Pierre Floras, Jeannemarie Lecomte, Anne-marie Bidabe, Jean-marie Caille, Guy L Simonnet, Michel Sabathie
    Abstract:

    The side effects in myelography are well known and frequently observed. The most common are headache, nausea, and vomit-ing. In this study, a rather new compound, Thiorphan, was examined, which displays an anti nociceptive activity by inhibit-ing Enkephalinase activity. Forty-two patients received intrave-nous infusions of Thiorphan before myelography. Another 42 patients were in a control group, and Thiorphan was not admin-istered. In the treated group, postmyelographic headache was found in 24 % (versus 52 % in the control group). Nausea and vomiting were never seen. Low back pain or sciatica was dimin-ished in 33 % of cases. Enkephalin levels in cerebrospinal fluid were measured by a radioreceptor-assay method in both groups without any correlation. Side effects in myelography are well known and occur in about 50 % of patients [1-5]. The most common are headache, nausea

  • effects of acetorphan an antidiarrhoeal Enkephalinase Inhibitor on oro caecal and colonic transit times in healthy volunteers
    Alimentary Pharmacology & Therapeutics, 2007
    Co-Authors: J F Bergmann, P Baumer, S Chaussade, D Couturier, Jeancharles Schwartz, Jeannemarie Lecomte
    Abstract:

    Acetorphan is a potent Enkephalinase Inhibitor displaying antidiarrhoeal activity attributable to its intestinal antisecretory action mediated by endogenous enkephalins. The effect of acetorphan on digestive motility was studied in 12 healthy volunteers. Oro-caecal transit time was evaluated using the sulphasalazine/sulphapyridine method and colonic transit times using radiopaque markers. These measurements were successively performed after one week treatment with an antidiarrhoeal dose of acetorphan (100 mg t.d.s.) or placebo. There was no significant modification in transit time linked to acetorphan treatment: total oro-caecal times were 303 +/- 32 min vs. 287 +/- 27 min and colonic transit times 25.8 +/- 5.8 h vs. 31.3 +/- 5.5 h after acetorphan and placebo, respectively (means +/- S.E.M.). There was no significant modification either in right colonic, left colonic or rectosigmoid segmental transit times, or in the mean number of stools. These results, consistent with those from animal studies, confirm that, unlike classical antidiarrhoeal mu opiate receptor agonists, which act by delaying intestinal transit, acetorphan does not affect the transit. Antidiarrhoeal activity not accompanied by a delayed intestinal transit could have beneficial therapeutic consequences in the management of infectious diarrhoea. In addition, we show that the sulphasalazine and radiopaque markers methods can be simultaneously applied in the same study.

  • effects of racecadotril and loperamide on bacterial proliferation and on the central nervous system of the newborn gnotobiotic piglet
    Alimentary Pharmacology & Therapeutics, 2001
    Co-Authors: Yvonne Duvaliflah, P Baumer, H Berard, P Guillaume, P Raibaud, Y Joulin, Jeannemarie Lecomte
    Abstract:

    Methods The effects of 4 days of oral administration of different doses of two drugs, an Enkephalinase Inhibitor (the antisecretory agent, racecadotril) and a μ-receptor agonist (loperamide), on intestinal growth of a bacterial nonpathogenic strain (Escherichia coli E 404) and on the central nervous system (CNS) were compared in newborn gnotobiotic piglets. Results The E. coli content of the proximal jejunum (segment S1) and the E. coli ratio of stomach:segment S1 were similar in the racecadotril (20 mg/kg b.d., n = 5) and control groups. In contrast, in the loperamide group (1 mg/kg b.d., n = 4), the E. coli content of segment S1 and the E. coli ratio stomach:S1 were both significantly higher than with racecadotril or control (P = 0.04 and 0.005, respectively, for E. coli content; P = 0.05 and 0.03, respectively, for stomach:S1). There were no clinical signs of neurotoxicity and no deaths with racecadotril given orally at a high dose of 130 mg/kg b.d. (n = 5) – nearly 60 times the paediatric dosage. In contrast, an equivalent high dose of loperamide (5 mg/kg b.d.) resulted in death in three out of four piglets. Conclusions In contrast to loperamide, racecadotril did not induce bacterial overgrowth and did not produce central neurotoxicity.

  • racecadotril demonstrates intestinal antisecretory activity in vivo
    Alimentary Pharmacology & Therapeutics, 1999
    Co-Authors: M P Primi, P Baumer, H Berard, L Bueno, Jeannemarie Lecomte
    Abstract:

    Background Racecadotril (acetorphan), a potent Enkephalinase Inhibitor, protects endogenous enkephalins from degradation. Racecadotril exhibits experimental and clinical antidiarrhoeal activity without any effect on intestinal motility, suggesting selective antisecretory activity. The antisecretory effect of racecadotril was directly assessed in the present study. Methods A 1 m, jejunal, Thiry–Vella loop was created in six mongrel dogs, and water and ionic fluxes were evaluated during infusion (2 mL/min) of Tyrode solution labelled with 14C-polyethylene glycol. Fluxes were determined both in the basal state and 5–6 h after commencement of a 2-h infusion of cholera toxin (0.4 μg/mL). Racecadotril (10 mg/kg) or vehicle was given orally with and without prior intravenous administration of naloxone (0.1 mg/kg) or phentolamine (0.2 mg/kg). Results Basal absorption remained unchanged following racecadotril administration; however, racecadotril significantly decreased (P = 0.01) cholera toxin-induced water, sodium, and potassium hypersecretion, from 0.73 ± 0.15 to 0.37 ± 0.13 mL/min; from 125.0 ± 16.1 to 14.7 ± 9.5 μMol/min; and from 3.41 ± 0.66 to 1.66 ± 0.61 μMol/min, respectively. This antisecretory activity of racecadotril was suppressed by naloxone but not by phentolamine. Conclusions This study directly demonstrates the antisecretory activity of racecadotril in relation to the protection of endogenous enkephalins.

  • comparison of racecadotril and loperamide in children with acute diarrhoea
    Alimentary Pharmacology & Therapeutics, 1999
    Co-Authors: D Turck, H Berard, N Fretault, Jeannemarie Lecomte
    Abstract:

    Methods A multicentre, randomized, double-blind, double-placebo, parallel-group study was carried out to compare the efficacy, tolerability, and safety of racecadotril (100 mg three times daily) and loperamide (2 mg after each diarrhoeic stool) in 157 adults with acute diarrhoea. Patients were treated for 7 days or until recovery, if this took place earlier. Results Both groups of patients passed similar numbers (mean ± S.E.M.) of stools before recovery (3.5 ± 0.5 for racecadotril vs. 2.9 ± 0.4 for loperamide), and the duration of diarrhoea (mean ± S.E.M.) was similar in both groups (14.9 ± 2.0 h for racecadotril and 13.7 ± 2.2 h for loperamide). Both treatments reduced the incidence of associated symptoms and signs during the study, and both were similarly well tolerated. However, more patients on loperamide reported rebound constipation during treatment (18.7% vs. 9.8% with racecadotril). Conclusions The Enkephalinase Inhibitor, racecadotril, and the intestinal transit Inhibitor, loperamide, were similarly and rapidly effective in resolving the symptoms and associated signs of diarrhoea.

Martin Kavaliers - One of the best experts on this subject based on the ideXlab platform.

  • Sex differences in the antinociceptive effects of the Enkephalinase Inhibitor, SCH 34826.
    Pharmacology Biochemistry and Behavior, 1993
    Co-Authors: Martin Kavaliers, Duncan G. L. Innes
    Abstract:

    Abstract The effects of endogenous opioid peptides are limited by proteolytic enzymes such as endopeptidase 24.11 (“Enkephalinase”), which cleaves the Gly-Phe bonds in Met- and Leu-enkephalin. SCH 34826 {(S)-N-[n-[1-[(2,2- dimethyl -1,3- dioxolan -4- yl ) methoxy ] carbonyl ]-2- phenylethyl ]- l - phenyl-alanine-B-alanine } is a potent, highly specific, Enkephalinase Inhibitor that has marked analgesic effects in laboratory rodents. The present study compared the effects of SCH 34826 on nociception and restraint stress-induced opioid analgesia in reproductive adult male and female deer mice, Peromyscus maniculatus . SCH 34826 had significantly greater antinociceptive actions and facilitatory effects on stress-induced analgesia in male than female mice. These antinociceptive effects of SCH 34826 were reduced by the general opioid antagonist naloxone and completely blocked by the specific delta opioid receptor antagonist, ICI 174,864, and nonsignificantly affected by the mu and kappa opioid receptor antagonists, β-funaltrexamine and nor-binaltorphimine, respectively. These results show that there are sex differences in the effects of the Enkephalinase Inhibitor, SCH 34826, on opioid-mediated antinociception and that these sex differences are associated with delta opioid mechanisms.

  • antinociceptive effects of the Enkephalinase Inhibitor sch 34826 in the snail cepaea nemoralis
    Peptides, 1993
    Co-Authors: Lisa M. Saksida, Laurence A. Galea, Martin Kavaliers
    Abstract:

    Abstract In vertebrates the effects of endogenous opioid peptides are limited by proteolytic enzymes such as endopeptidase 24.11 (Enkephalinase), which cleaves the Gly-Phe bonds in both methionine- and leucine-enkephalin. SCH 34826 { (S)-N-[n- [1-[(2,2-dimethyl-1,3-dioxolan-4yl) methoxy]carbonyl]-2-phenylethyl]- l -phenyl-alanine-B-alanine} is a potent, highly specific, Enkephalinase Inhibitor that has marked analgesic effects in mammals. The present study examined the effects of SCH 34826 on opioid-mediated aversive thermal (nociceptive) responses of an invertebrate, the land snail, Cepaea nemoralis. SCH 34828 had significant, dose-related antinociceptive effects in Cepaea that were reduced by naloxone and completely blocked by the specific delta opiate antagonist, ICI-174,864, and only weakly affected by the specific kappa opiate antagonist nor-binaltrophimine. These findings with SCH 34826 suggest that an Enkephalinase similar to that in vertebrates is present and involved in the mediation of opioid (enkephalin) activity in the snail, Cepaea.

  • antinociceptive effects of the Enkephalinase Inhibitor sch 34826 in the snail cepaea nemoralis
    Peptides, 1993
    Co-Authors: Lisa M. Saksida, Laurence A. Galea, Martin Kavaliers
    Abstract:

    In vertebrates the effects of endogenous opioid peptides are limited by proteolytic enzymes such as endopeptidase 24.11 (Enkephalinase), which cleaves the Gly-Phe bonds in both methionine- and leucine-enkephalin. SCH 34826 ((S)-N-[n-[1-[(2,2-dimethyl-1,3-dioxolan-4yl) methoxy]carbonyl]-2-phenylethyl]-L-phenylalanine-B-alanine) is a potent, highly specific, Enkephalinase Inhibitor that has marked analgesic effects in mammals. The present study examined the effects of SCH 34826 on opioid-mediated aversive thermal (nociceptive) response of an invertebrate, the land snail, Cepaea nemoralis. SCH 34828 had significant, dose-related antinociceptive effects in Cepaea that were reduced by naloxone and completely blocked by the specific data opiate antagonist, ICI-174,864, and only weakly affected by the specific kappa opiate antagonist nor-binaltrophimine. These findings with SCH 34826 suggest that an Enkephalinase similar to that in vertebrates is present and involved in the mediation of opioid (enkephalin) activity in the snail, Cepaea.

Lisa M. Saksida - One of the best experts on this subject based on the ideXlab platform.

  • antinociceptive effects of the Enkephalinase Inhibitor sch 34826 in the snail cepaea nemoralis
    Peptides, 1993
    Co-Authors: Lisa M. Saksida, Laurence A. Galea, Martin Kavaliers
    Abstract:

    Abstract In vertebrates the effects of endogenous opioid peptides are limited by proteolytic enzymes such as endopeptidase 24.11 (Enkephalinase), which cleaves the Gly-Phe bonds in both methionine- and leucine-enkephalin. SCH 34826 { (S)-N-[n- [1-[(2,2-dimethyl-1,3-dioxolan-4yl) methoxy]carbonyl]-2-phenylethyl]- l -phenyl-alanine-B-alanine} is a potent, highly specific, Enkephalinase Inhibitor that has marked analgesic effects in mammals. The present study examined the effects of SCH 34826 on opioid-mediated aversive thermal (nociceptive) responses of an invertebrate, the land snail, Cepaea nemoralis. SCH 34828 had significant, dose-related antinociceptive effects in Cepaea that were reduced by naloxone and completely blocked by the specific delta opiate antagonist, ICI-174,864, and only weakly affected by the specific kappa opiate antagonist nor-binaltrophimine. These findings with SCH 34826 suggest that an Enkephalinase similar to that in vertebrates is present and involved in the mediation of opioid (enkephalin) activity in the snail, Cepaea.

  • antinociceptive effects of the Enkephalinase Inhibitor sch 34826 in the snail cepaea nemoralis
    Peptides, 1993
    Co-Authors: Lisa M. Saksida, Laurence A. Galea, Martin Kavaliers
    Abstract:

    In vertebrates the effects of endogenous opioid peptides are limited by proteolytic enzymes such as endopeptidase 24.11 (Enkephalinase), which cleaves the Gly-Phe bonds in both methionine- and leucine-enkephalin. SCH 34826 ((S)-N-[n-[1-[(2,2-dimethyl-1,3-dioxolan-4yl) methoxy]carbonyl]-2-phenylethyl]-L-phenylalanine-B-alanine) is a potent, highly specific, Enkephalinase Inhibitor that has marked analgesic effects in mammals. The present study examined the effects of SCH 34826 on opioid-mediated aversive thermal (nociceptive) response of an invertebrate, the land snail, Cepaea nemoralis. SCH 34828 had significant, dose-related antinociceptive effects in Cepaea that were reduced by naloxone and completely blocked by the specific data opiate antagonist, ICI-174,864, and only weakly affected by the specific kappa opiate antagonist nor-binaltrophimine. These findings with SCH 34826 suggest that an Enkephalinase similar to that in vertebrates is present and involved in the mediation of opioid (enkephalin) activity in the snail, Cepaea.

Jean Costentin - One of the best experts on this subject based on the ideXlab platform.

  • Effects of thiorphan, bestatin and a novel metallopeptidase Inhibitor JMV 390-1 on the recovery of neurotensin and neuromedin N released from mouse hypothalamus.
    Neuroscience letters, 1992
    Co-Authors: Patrick Kitabgi, Jean Costentin, I. Dubuc, D Nouel, Jean-claude Cuber, Hélène Fulcrand, Silvie Doulut, Marc Rodriguez, Jean Martinez
    Abstract:

    Abstract The effects of the endopeptidase 24.11 (‘Enkephalinase’) Inhibitor thiorphan, the aminopeptidase Inhibitor bestatin and a novel metallopeptidase Inhibitor JMV 390-1 on the K + -evoked release of immunoreactive neurotensin and neuromedin N (iNT and iNN) from mouse hypothalamic slices were examined. (JMV 390-1 inhibits several metallopeptidases including endopeptidases 24.11, 24.15 and 24.16, and aminopeptidase N equipotently with K i values around 50 nM.) Thiorphan increased the recovery of released iNT nearly 2-fold and had no effect on iNN. Bestatin produced a 4-fold increase in iNN recovery and was inactive on iNT. Finally, iNT and iNN recoveries were increased up to 4- and 5-fold, respectively, by JMV 390-1. These results show that in the mouse hypothalamus endopeptidase 24.11 participates with other metalloendopeptidases to the degradation of endogenously released NT while endogenously released NN is principally degraded by aminopeptidase(s).

  • desensitization of μ opioid receptors does not modify the analgesia induced by an Enkephalinase Inhibitor
    European Journal of Pharmacology, 1991
    Co-Authors: Rachida Bousselmame, Adina T Michaeltitus, Jean Costentin
    Abstract:

    Abstract Acetorphan, an Enkephalinase Inhibitor, or morphine was injected in mice which had received saline or morphine (32 mg/kg s.c. twice a day on 8 consecutive days) chronically. In the hot-plate test, the analgesia (increase in jump latency) induced by morphine (2 mg/kg i.p.) or by the μ selective opioid agonist, [D-Ala2,N-Me-Phe4, Gly5ol]enkephalin (DAGO) (1.5, 3 or 6 ng/mouse i.c.v.), was significant in the saline group but was strongly decreased in morphine-pretreated mice. In contrast the analgesic effect of acetorphan (5 mg/kg i.v.) or of the δ selective opioid agonist [D-Pen2,D-Pen-5]enkephalin (DPDPE) (0.75, 1.5 or 3 μg/mouse i.c.v.) was similar in both groups. These results suggest that the enkephalins protected by acetorphan act on the δ receptor site to produce antinociception.

  • Chronic inhibition of Enkephalinase induces changes in the antinociceptive and locomotor effects of the Enkephalinase Inhibitor acetorphan in rats.
    Neuropharmacology, 1991
    Co-Authors: Rachida Bousselmame, M. L. Eustache, Adina T. Michael-titus, Jean Costentin
    Abstract:

    Abstract The Enkephalinase Inhibitor thiorphan was infused intracerebroventricularly in rats during 14 days (25 μg/5 μ1/hr), inducing an average inhibition of cerebral Enkephalinase of about 65%. Animals were tested during the infusion for their response to acetorphan, a parenterally active derivative of thiorphan. When administered intravenously on day 8 of the infusion, acetorphan (5 mg/kg) significantly increased locomotion in chronic saline-infused rats but not in animals receiving thiorphan. Furthermore, when injected at the same dose on day 10, acetorphan did not modify the latency to jump, in the hot plate test, in thiorphan-treated rats, whereas it elicited a significant analgesia in chronic saline-treated controls. These data show that the effects induced by the administration of an Enkephalinase Inhibitor were diminished after a period of chronic inhibition of the enzyme, suggesting the development of tolerance.

P Baumer - One of the best experts on this subject based on the ideXlab platform.

  • effects of acetorphan an antidiarrhoeal Enkephalinase Inhibitor on oro caecal and colonic transit times in healthy volunteers
    Alimentary Pharmacology & Therapeutics, 2007
    Co-Authors: J F Bergmann, P Baumer, S Chaussade, D Couturier, Jeancharles Schwartz, Jeannemarie Lecomte
    Abstract:

    Acetorphan is a potent Enkephalinase Inhibitor displaying antidiarrhoeal activity attributable to its intestinal antisecretory action mediated by endogenous enkephalins. The effect of acetorphan on digestive motility was studied in 12 healthy volunteers. Oro-caecal transit time was evaluated using the sulphasalazine/sulphapyridine method and colonic transit times using radiopaque markers. These measurements were successively performed after one week treatment with an antidiarrhoeal dose of acetorphan (100 mg t.d.s.) or placebo. There was no significant modification in transit time linked to acetorphan treatment: total oro-caecal times were 303 +/- 32 min vs. 287 +/- 27 min and colonic transit times 25.8 +/- 5.8 h vs. 31.3 +/- 5.5 h after acetorphan and placebo, respectively (means +/- S.E.M.). There was no significant modification either in right colonic, left colonic or rectosigmoid segmental transit times, or in the mean number of stools. These results, consistent with those from animal studies, confirm that, unlike classical antidiarrhoeal mu opiate receptor agonists, which act by delaying intestinal transit, acetorphan does not affect the transit. Antidiarrhoeal activity not accompanied by a delayed intestinal transit could have beneficial therapeutic consequences in the management of infectious diarrhoea. In addition, we show that the sulphasalazine and radiopaque markers methods can be simultaneously applied in the same study.

  • effects of racecadotril and loperamide on bacterial proliferation and on the central nervous system of the newborn gnotobiotic piglet
    Alimentary Pharmacology & Therapeutics, 2001
    Co-Authors: Yvonne Duvaliflah, P Baumer, H Berard, P Guillaume, P Raibaud, Y Joulin, Jeannemarie Lecomte
    Abstract:

    Methods The effects of 4 days of oral administration of different doses of two drugs, an Enkephalinase Inhibitor (the antisecretory agent, racecadotril) and a μ-receptor agonist (loperamide), on intestinal growth of a bacterial nonpathogenic strain (Escherichia coli E 404) and on the central nervous system (CNS) were compared in newborn gnotobiotic piglets. Results The E. coli content of the proximal jejunum (segment S1) and the E. coli ratio of stomach:segment S1 were similar in the racecadotril (20 mg/kg b.d., n = 5) and control groups. In contrast, in the loperamide group (1 mg/kg b.d., n = 4), the E. coli content of segment S1 and the E. coli ratio stomach:S1 were both significantly higher than with racecadotril or control (P = 0.04 and 0.005, respectively, for E. coli content; P = 0.05 and 0.03, respectively, for stomach:S1). There were no clinical signs of neurotoxicity and no deaths with racecadotril given orally at a high dose of 130 mg/kg b.d. (n = 5) – nearly 60 times the paediatric dosage. In contrast, an equivalent high dose of loperamide (5 mg/kg b.d.) resulted in death in three out of four piglets. Conclusions In contrast to loperamide, racecadotril did not induce bacterial overgrowth and did not produce central neurotoxicity.

  • racecadotril demonstrates intestinal antisecretory activity in vivo
    Alimentary Pharmacology & Therapeutics, 1999
    Co-Authors: M P Primi, P Baumer, H Berard, L Bueno, Jeannemarie Lecomte
    Abstract:

    Background Racecadotril (acetorphan), a potent Enkephalinase Inhibitor, protects endogenous enkephalins from degradation. Racecadotril exhibits experimental and clinical antidiarrhoeal activity without any effect on intestinal motility, suggesting selective antisecretory activity. The antisecretory effect of racecadotril was directly assessed in the present study. Methods A 1 m, jejunal, Thiry–Vella loop was created in six mongrel dogs, and water and ionic fluxes were evaluated during infusion (2 mL/min) of Tyrode solution labelled with 14C-polyethylene glycol. Fluxes were determined both in the basal state and 5–6 h after commencement of a 2-h infusion of cholera toxin (0.4 μg/mL). Racecadotril (10 mg/kg) or vehicle was given orally with and without prior intravenous administration of naloxone (0.1 mg/kg) or phentolamine (0.2 mg/kg). Results Basal absorption remained unchanged following racecadotril administration; however, racecadotril significantly decreased (P = 0.01) cholera toxin-induced water, sodium, and potassium hypersecretion, from 0.73 ± 0.15 to 0.37 ± 0.13 mL/min; from 125.0 ± 16.1 to 14.7 ± 9.5 μMol/min; and from 3.41 ± 0.66 to 1.66 ± 0.61 μMol/min, respectively. This antisecretory activity of racecadotril was suppressed by naloxone but not by phentolamine. Conclusions This study directly demonstrates the antisecretory activity of racecadotril in relation to the protection of endogenous enkephalins.

  • the Enkephalinase Inhibitor acetorphan in acute diarrhoea a double blind controlled clinical trial versus loperamide
    Scandinavian Journal of Gastroenterology, 1993
    Co-Authors: J Roge, J C Schwartz, P Baumer, H Berard, Jeannemarie Lecomte
    Abstract:

    The antidiarrhoeal properties of acetorphan, an Inhibitor of Enkephalinase (EC 3.4.24.11) that prevents endogenous enkephalin degradation, and loperamide, a mu opiate receptor agonist, were compared. The double-blind study included 69 patients with acute diarrhoea of presumed infectious origin, allocated at random to two parallel groups. Acetorphan and loperamide were both rapidly and similarly effective, diarrhoea resolving in both cases in nearly 2 days. With acetorphan, however, abdominal distension vanished significantly more rapidly, and reactive constipation was less frequent (8% versus 31% with loperamide). These differences can be accounted for by the distinct mechanisms of antidiarrhoeal activity of the two drugs—that is, primary antitransit effect for loperamide and antisecretory activity for acetorphan.

  • effects of acetorphan an Enkephalinase Inhibitor on experimental and acute diarrhoea
    Gut, 1992
    Co-Authors: P Baumer, J C Schwartz, Danquechin E Dorval, J Bertrand, J M Vetel, Jeannemarie Lecomte
    Abstract:

    Acetorphan is an orally active Inhibitor of Enkephalinase (EC 3.4.24.11) with antidiarrhoeal activity in rodents apparently through protection of endogenous enkephalins and a purely antisecretory mechanism. Its antidiarrhoeal activity in man was assessed in an experimental model of cathartic induced secretory diarrhoea as well as in acute diarrhoea of presumed infectious origin. In six healthy volunteers receiving castor oil and pretreated with acetorphan or placebo in a crossover controlled trial, the drug significantly decreased the number and weight of stools passed during 24 hours. About 200 outpatients with severe acute diarrhoea (more than five stools per day) were included in a randomised double blind study of acetorphan against placebo. The significant antidiarrhoeal activity of acetorphan was established using a variety of criteria: (i) the duration of both diarrhoea and treatment were diminished; (ii) no acetorphan treated patient withdrew from the study whereas five dropped out because of worsening in the placebo group; (iii) the frequency of symptoms associated with diarrhoea--for example, abdominal pain or distension, nausea and anorexia--remaining after two weeks was nearly halved; (iv) using visual analogue scales acetorphan treatment was found more effective than placebo by both investigators and patients. There was statistically no significant difference between acetorphan and placebo in respect of side effects, particularly constipation, which often accompanies the antidiarrhoeal activity of mu opioid receptor agonists this difference is attributable to the lack of antipropulsive activity of acetorphan in man. The efficacy and tolerance of acetorphan suggest that Enkephalinase inhibition may represent a novel therapeutic approach for the symptomatic management of acute secretory diarrhoea without impairing intestinal transit.