Neutropenia Associated With Metiamide

Forrest, J. A. H.; Shearman, D. J. C.; Spence, Rebecca; Celestin, Louis-Cyril

doi:10.1016/s0140-6736(75)91305-7

Cited by 74 publications

(19 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In chronic toxicity tests, using doses of metiamide at least twenty times the orally effective dose in the dog, some animals developed kidney damage and agranulocytosis (Brimblecombe, Duncan & Walker, 1973). Two patients being treated with metiamide developed a readily reversible granulocytopenia (Forrest, Shearman, Spence & Celestin, 1975). Brimblecombe, Duncan, Durant, Emmett, Ganellin & Parsons (1975) that in 90-day chronic toxicity tests in the rat and dog no renal or haematological abnormalities were observed.…”

Section: Introduction Methodsmentioning

confidence: 99%

“…Clinically, metiamide gives marked symptomatic relief to patients with peptic ulcer (Pounder, Williams, Milton-Thompson & Misiewicz, 1975) and healing of recalcitrant multiple ulcers has been reported following treatment with metiamide (Haggie, Clark, Black & Wylie, 1975;Thompson, Venables, Miller, Reed, Sanders, Grund & Blair, 1975). The only significant side effects which have been reported following treatment with metiamide have been two cases of a readily reversible granulocytopenia (Forrest et al, 1975). As a result of these cases, clinical trials with metiamide have been limited to the more seriously ill patient with proven peptic ulcer resistant to other therapeutic treatment.…”

Section: Metabolismmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacological evaluation of cimetidine, a new histamine H2‐receptor antagonist, in healthy man.

Burland¹,

Duncan²,

Hesselbo³

et al. 1975

Brit J Clinical Pharma

195

View full text Add to dashboard Cite

Cimetidine, a new H2‐receptor antagonist, was safely administered to eighteen healthy man by the intravenous, intraduodenal or oral route. 2 When gastric secretion was maximally stimulated by either histamine or pentagastrin, the simultaneous administration of cimetidine produced marked inhibition of both acid and pepsin secretion. 3 Cimetidine was well absorbed by mouth and had a blood half‐life of 2 hours. 4 Cimetidine was rapidly excreted via the kidneys and about 70% of the excreted material was unchanged drug. 5 Clinical evaluation of cimetidine in patients with peptic ulceration is recommended.

show abstract

Section: Introduction Methodsmentioning

confidence: 99%

Section: Metabolismmentioning

confidence: 99%

Pharmacological evaluation of cimetidine, a new histamine H2‐receptor antagonist, in healthy man.

Burland¹,

Duncan²,

Hesselbo³

et al. 1975

Brit J Clinical Pharma

195

View full text Add to dashboard Cite

show abstract

“…5) are also associated with significant incidences of immune-mediated agranulocytosis. The histamine H2 receptor antagonist metiamide was suspended from clinical trials for the treatment of peptic ulcers because an unacceptable number of patients developed agranulocytosis (Forrest et al, 1975). From a structure-toxicity perspective, cimetidine (see Fig.…”

Section: Perspectivementioning

confidence: 99%

Immune-Mediated Agranulocytosis Caused by the Cocaine Adulterant Levamisole: A Case for Reactive Metabolite(s) Involvement

Wolford

McDonald²,

Eng³

et al. 2012

Drug Metabolism and Disposition

View full text Add to dashboard Cite

ABSTRACT:The United States Public Health Service Administration is alerting medical professionals that a substantial percentage of cocaine imported into the United States is adulterated with levamisole, a veterinary pharmaceutical that can cause blood cell disorders such as severe neutropenia and agranulocytosis. Levamisole was previously approved in combination with fluorouracil for the treatment of colon cancer; however, the drug was withdrawn from the U.S. market in 2000 because of the frequent occurrence of agranulocytosis. The detection of autoantibodies such as antithrombin (lupus anticoagulant) and an increased risk of agranulocytosis in patients carrying the human leukocyte antigen B27 genotype suggest that toxicity is immune-mediated. In this perspective, we provide an historical account of the levamisole/cocaine story as it first surfaced in 2008, including a succinct review of levamisole pharmacology, pharmacokinetics, and preclinical/clinical evidence for levamisole-induced agranulocytosis. Based on the available information on levamisole metabolism in humans, we propose that reactive metabolite formation is the rate-limiting step in the etiology of agranulocytosis associated with levamisole, in a manner similar to other drugs (e.g., propylthiouracil, methimazole, captopril, etc.) associated with blood dyscrasias. Finally, considering the toxicity associated with levamisole, we propose that the 2,3,5,6-tetrahydroimidazo[2,1-b]thiazole scaffold found in levamisole be categorized as a new structural alert, which is to be avoided in drug design.

show abstract

“…Out of 700 patients treated with metiamide, however, there were a few cases of granulocytopenia which, although reversible, limited the amount of clinical work [21]. The question now arose as to whether the granulocytopenia was due to H 2 -receptor blockade or whether it was an effect caused idiosyncratically by the chemical structure.…”

Section: Designing a Drug (Cimetidine) To Block Histamine H 2 -Receptorsmentioning

confidence: 99%

Personal reflections on Sir James Black (1924–2010) and histamine

Ganellin

2010

Inflamm. Res.

View full text Add to dashboard Cite

Sir James Black, Nobel laureate (1988), became interested in the role of histamine in gastric acid secretion in the early 1950s. In 1964, he joined the pharmaceutical company Smith Kline and French Laboratories at their English subsidiary to seek a new type of antagonist that would block those actions of histamine that were not blocked by mepyramine. No such compound was known and working with medicinal chemists it took four years to discover a lead compound. Further work provided the compound burimamide, which was used to define histamine H(2) receptors in 1972 for the first time, and to verify the action in human volunteers. Subsequent work led to the drug metiamide, which was withdrawn during early clinical trials. This was replaced by cimetidine, which was launched in 1977, as the first histamine H(2)-receptor antagonist and which revolutionized the treatment of peptic ulcer disease. The characterisation of a second type of histamine receptor revitalised interest in histamine and led to many later studies on the role of histamine in inflammation.

show abstract

Neutropenia Associated With Metiamide

Cited by 74 publications

References 1 publication

Pharmacological evaluation of cimetidine, a new histamine H2‐receptor antagonist, in healthy man.

Pharmacological evaluation of cimetidine, a new histamine H2‐receptor antagonist, in healthy man.

Immune-Mediated Agranulocytosis Caused by the Cocaine Adulterant Levamisole: A Case for Reactive Metabolite(s) Involvement

Personal reflections on Sir James Black (1924–2010) and histamine

Contact Info

Product

Resources

About