SUMMARY Gastrointestinal motor function in patients with primary anorexia nervosa has rarely been investigated. We studied oesophageal motor activity in 30 consecutive patients meeting standard diagnostic criteria for primary anorexia nervosa (Feighner et al; DSM III). Seven were found to suffer from achalasia instead of primary anorexia nervosa, one from diffuse oesophageal spasm and one from severe gastro-oesophageal reflux and upper oesophageal sphincter hypertonicity, while partly non-propulsive and repetitive high amplitude, long duration contractions prevailed in the lower oesophagus of another six. In four patients with oesophageal dysmotility not responding to therapy and in 12 of 15 patients with normal oesophageal manometry, gastric emptying of a semisolid meal was studied. Emptying was normal in only three but markedly delayed in 13 cases (half emptying times 97-330 min, median: 147 min, as compared with 21-119 min, median: 47 min, in 24 healthy controls). In eight patients, the effects of domperidone 10 mg iv and placebo were compared under random double blind conditions. Half emptying times were shortened significantly (p<0.01) by domperidone. Conclusions: (1) symptoms of disordered upper gastrointestinal motor activity may be mistaken as indicating primary anorexia nervosa; (2) clinical evaluation of patients with presumed primary anorexia nervosa should rule out the possibility that disordered oesophageal motor activity underlies the symptoms; (3) delayed gastric emptying is a frequent feature in primary anorexia nervosa and might be returned to normal with domperidone.

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1 Antitussive, antinociceptive and respiratory depressant effects of codeine, morphine and H.Tyr.DArg.Gly.Phe(4-NO2) Pro.NH2 (compound BW443C) were investigated in unanaesthetized guineapigs. Antagonism of the antitussive and antinociceptive effects was investigated by the use of nalorphine and N-methylnalorphine. Naloxone was used to antagonize respiratory depression.2 Antitussive ED50s (with 95% confidence limits) for inhibition of cough induced by citric acid vapour were for codeine, morphine and BW443C respectively, 9.1(5.8-15), 1.3(0.7-2.4) and 1.2(0.6-2.6) mg kg-' s.c. and 8.7(4.2-12), 1.6(1.2-1.9) and 0.67(0.002-3.3) mg kg-', i.v. The antitussive effects of subcutaneous codeine (25mg kg-') morphine (8.1 mg kg-') and BW443C (2.5mg kg-') were significantly antagonized by subcutaneous nalorphine (3.0 mg kg-') and N-methylnalorphine (3.0mg kg-').3 In the multiple toe-pinch test, the antinociceptive ED5s (with 95% confidence limits) of codeine and morphine were 18(16-22) and 2.3(0.4-4.3) mg kg-', s.c., respectively. Compound BW443C was ineffective in doses of 2.5 and 10 mg kg-' s.c., a result consistent with its lacking penetration into the CNS. Subcutaneous nalorphine (3.0mg kg-') antagonized the antinociceptive action of codeine (25mg kg-') and morphine (8.1 mg kg-'). In contrast, N-methylnalorphine (3.0mg kg-') had no significant effect on the antinociceptive action of codeine and morphine, suggesting lack of penetration of the CNS by N-methylnalorphine.4 At doses near to the i.v. ED50 values for the antitussive activity, morphine (1.5 mg kg-', i.v.) and codeine (10mg kg-', i.v.) caused small but significant depressions of ventilation (7.0 ± 2.3% and 16.5 ± 8.4% respectively). Higher doses of morphine (10, 30 and 60mg kg-',i.v.) caused further doserelated depression of ventilation (9.6 ± 5.3%, 22.4 ± 6.2% and 36.2 ± 9.6% respectively) whereas codeine (30 and 60 mg kg-' i.v.) caused stimulation of ventilation which was marked (191.3 ± 43.9%) at 60 mg kg-'. 5 Compound BW443C in doses of 1 or 10mgkg-',i.v. (approximately equal to, and 10 times the EDo for antitussive activity) did not cause significant depression of ventilation. Only at higher doses of 30 and 60mg kg-', i.v. was there a significant decrease in minute volume (13.1 ± 6.8% and 15.9 ± 1.89% respectively). The depression of ventilation caused by either BW443C (60mg kg- ', i.v.) or morphine (60mg kg-', i.v.) was prevented by pretreatment with naloxone (3mg kg- ', i.v.) administered 15 min before morphine or BW443C. 6 These results in the guinea-pig support the hypothesis that the antitussive action of the opiates codeine and morphine and the opioid pentapeptide BW443C do not require penetration of these drugs into the CNS.

SUMMARY Cyclotropium bromide, a new antimuscarinic agent, inhibits gastrointestinal motility in animals at lower doses than those required to inhibit gastric acid secretion and salivation. In man, cyclotropium bromide suppresses fasting and meal stimulated colonic motility. This study investigated the effects of single oral doses of 60 mg cyclotropium bromide, 60 mg hyoscine N-butylbromide and placebo on gastric emptying and on antral motor activity. Twenty four healthy men (mean age 25 years) participated in three experiments one week apart. The drugs were administered, in random double blind fashion, 30 minutes before the ingestion of a semisolid test meal labelled with 74 MBq (2 mCi) 99mTc sulphur colloid. A gamma camera coupled to a computer monitored gastric emptying together with amplitude, frequency, and propagation velocity of antral contractions. Cyclotropium bromide and, to a lesser degree, hyoscine N-butylbromide delayed gastric emptying and reduced contraction amplitude, but did not affect frequency and propagation velocity of antral contractions. Cyclotropium bromide was significantly more active than hyoscine N-butylbromide; the effects of hyoscine N-butylbromide differed significantly from placebo. Antral contractile activity was present all the time. After cyclotropium bromide, there was a significant correlation between antral contraction amplitude and gastric emptying. No adverse side effects occurred with any one treatment. In conclusion, cyclotropium bromide markedly inhibits gastric emptying and reduces antral contraction amplitude.Cyclotropium bromide (CTB; Helopharm, Berlin) is a quarternary ammonium compound exhibiting differential activities at muscarinic receptor sites. In that rat, cyclotropium bromide administered subcutaneously or intraduodenally is 10 times less active in reducing gastric acid secretion than atropine, whereas its antagonistic effect on acetylcholine induced spasms of the guinea pig rectum is 7.3 times and the effect against pilocarpine induced spasms 2-8 times stronger than that of atropine.Tachycardia, mydriasis, and inhibition of salivary secretion occur only at high dosages (Helopharm, Berlin, unpublished data). In man it has been shown that a single oral dose of 60 mg cyclotropium bromide inhibits fasting and meal stimulated colonic

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