Abstract
Eight healthy male volunteers participated in a single-blind, random allocation, crossover, comparison of intravenous metoclopramide (10 mg), the peripherally acting, gastrointestinal stimulant BRL 20627 (10 mg) and saline. The central nervous system effects were assessed by quantitative electroencephalography (EEG) and by visual analogue scales. Gastric motility and emptying were assessed by epigastric impedance. Metoclopramide increased the EEG amplitude by 10.4% (a statistically significant, P less than 0.05, effect) and increased frequencies above 22 Hz, whereas both BRL 20627 and placebo had only minor effect on the EEG frequencies and slightly decreased the EEG amplitude. Ratings on visual analogue scales showed that metoclopramide caused statistically significant (P less than 0.01 difference from placebo) restlessness and slight but significantly less (P less than 0.05 difference from placebo) feeling of happiness. Epigastic impedance changes indicated that both metoclopramide and BRL 20627 increased gastric contractile activity, but the rate of gastric emptying was not significantly altered by either drug although it tended to be shortened following metoclopramide but not BRL 20627 treatment. It is concluded that since the published animal data show that BRL 20627 has only weak dopamine antagonistic properties this study further implicates dopamine receptor blockade in the akathisia but not in the gastric effect of metoclopramide.
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Selected References
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- Bateman D. N. Clinical pharmacokinetics of metoclopramide. Clin Pharmacokinet. 1983 Nov-Dec;8(6):523–529. doi: 10.2165/00003088-198308060-00003. [DOI] [PubMed] [Google Scholar]
- Bateman D. N., Kahn C., Mashiter K., Davies D. S. Pharmacokinetic and concentration-effect studies with intravenous metoclopramide. Br J Clin Pharmacol. 1978 Nov;6(5):401–407. doi: 10.1111/j.1365-2125.1978.tb04604.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Costall B., Gunning S. J., Naylor R. J., Simpson K. H. A central site of action for benzamide facilitation of gastric emptying. Eur J Pharmacol. 1983 Jul 22;91(2-3):197–205. doi: 10.1016/0014-2999(83)90465-x. [DOI] [PubMed] [Google Scholar]
- Fontaine J., Reuse J. Pharmacological analysis of the effects of substituted benzamides on the isolated guinea-pig ileum. Study of metoclopramide, sulpiride, bromopride, tiapride and sultopride. Arch Int Pharmacodyn Ther. 1978 Sep;235(1):51–61. [PubMed] [Google Scholar]
- Giger M. Toxische Wirkungen von Metoclopramid. Schweiz Rundsch Med Prax. 1975 Jul 22;64(29):930–932. [PubMed] [Google Scholar]
- Harrington R. A., Hamilton C. W., Brogden R. N., Linkewich J. A., Romankiewicz J. A., Heel R. C. Metoclopramide. An updated review of its pharmacological properties and clinical use. Drugs. 1983 May;25(5):451–494. doi: 10.2165/00003495-198325050-00002. [DOI] [PubMed] [Google Scholar]
- Jungmann E., Schöffling K. Akathisia and metoclopramide. Lancet. 1982 Jul 24;2(8291):221–221. doi: 10.1016/s0140-6736(82)91077-7. [DOI] [PubMed] [Google Scholar]
- Kane J. M., Smith J. M. Tardive dyskinesia: prevalence and risk factors, 1959 to 1979. Arch Gen Psychiatry. 1982 Apr;39(4):473–481. doi: 10.1001/archpsyc.1982.04290040069010. [DOI] [PubMed] [Google Scholar]
- Karp J. M., Perkel M. S., Hersh T., McKinney A. S. Metoclopramide treatment of tardive dyskinesia. JAMA. 1981 Oct 23;246(17):1934–1935. [PubMed] [Google Scholar]
- Kilbinger H., Kruel R., Pfeuffer-Friederich I., Wessler I. The effects of metoclopramide on acetylcholine release and on smooth muscle response in the isolated guinea-pig ileum. Naunyn Schmiedebergs Arch Pharmacol. 1982 Jun;319(3):231–238. doi: 10.1007/BF00495871. [DOI] [PubMed] [Google Scholar]
- Masso J. L., Roberts D. J. Comparison of the potencies of clebopride and other substituted benzamide drugs on isolated gastrointestinal tract of the guinea-pig and rat. J Pharm Pharmacol. 1980 Oct;32(10):727–728. doi: 10.1111/j.2042-7158.1980.tb13054.x. [DOI] [PubMed] [Google Scholar]
- McClelland G. R., Raptopoulos P. EEG and blood level of the potential antidepressant paroxetine after a single oral dose to normal volunteers. Psychopharmacology (Berl) 1984;83(4):327–329. doi: 10.1007/BF00428539. [DOI] [PubMed] [Google Scholar]
- McClelland G. R., Sutton J. A. Epigastric impedance: a non-invasive method for the assessment of gastric emptying and motility. Gut. 1985 Jun;26(6):607–614. doi: 10.1136/gut.26.6.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McClelland G. R., Sutton J. A. Pilot investigation of the quantitative EEG and clinical effects of ketazolam and the novel antiemetic nonabine in normal subjects. Psychopharmacology (Berl) 1985;85(3):306–308. doi: 10.1007/BF00428192. [DOI] [PubMed] [Google Scholar]
- Nakra B. R., Bond A. J., Lader M. H. Comparative psychotropic effects of metoclopramide and prochlorperazine in normal subjects. J Clin Pharmacol. 1975 May-Jun;15(5-6):449–454. doi: 10.1002/j.1552-4604.1975.tb02368.x. [DOI] [PubMed] [Google Scholar]
- Robinson O. P. Metoclopramide--side effects and safety. Postgrad Med J. 1973 Jul;49 (Suppl 4):suppl 4–4:80. [PubMed] [Google Scholar]
- Strum S. B., McDermed J. E. Treatment of side effects in patients receiving Iv metoclopramide. Cancer Treat Rep. 1983 Nov;67(11):1049–1050. [PubMed] [Google Scholar]
- Tarsy D., Parkes J. D., Marsden C. D. Metoclopramide and pimozide in Parkinson's disease and levodopa-induced dyskinesias. J Neurol Neurosurg Psychiatry. 1975 Apr;38(4):331–335. doi: 10.1136/jnnp.38.4.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wachtel R. E. Effects of some depressant drugs on synaptic responses to glutamate at the crayfish neuromuscular junction. Br J Pharmacol. 1984 Oct;83(2):387–391. doi: 10.1111/j.1476-5381.1984.tb16498.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wiholm B. E., Mortimer O., Boethius G., Häggström J. E. Tardive dyskinesia associated with metoclopramide. Br Med J (Clin Res Ed) 1984 Feb 18;288(6416):545–547. doi: 10.1136/bmj.288.6416.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
