The Interaction of Ammonium, Sulfonium, and Sulfide Analogues of Metoclopramide with the Dopamine D2 Receptor

Marc W. Harrold, Anong Sriburi, Kazuhisa Matsumoto, Duane Miller, Tahira Farooqui, Norman Uretsky

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

A series of permanently charged ammonium and sulfonium analogues of metoclopramide as well as a permanently uncharged sulfide analogue were synthesized and evaluated for their ability to inhibit apomorphine-induced responses on mouse striatal slices. Three of the four permanently charged analogues were found to inhibit apomorphine's effects, although at higher concentrations than either metoclopramide or its dimethyl analogue. In contrast, the sulfide analogue was inactive at concentrations up to 100 µM. These findings are consistent with earlier studies of chlorpromazine and sulpiride analogues and provide further evidence that dopamine antagonists bind in their charged molecular forms to anionic sites on the D2 receptor. Further, the results of this study in conjunction with those of our earlier sulpiride study would seem to indicate that differences in the biological profiles of metoclopramide, a type 1 benzamide useful as a gastric prokinetic agent, and sulpiride, a type 2 benzamide useful for its antipsychotic effects, are not due to any appreciable differences in the binding of the basic nitrogen atom of these molecules.

Original languageEnglish (US)
Pages (from-to)3166-3170
Number of pages5
JournalJournal of Medicinal Chemistry
Volume36
Issue number21
DOIs
StatePublished - Jan 1 1993
Externally publishedYes

Fingerprint

Sulpiride
Metoclopramide
Dopamine D2 Receptors
Apomorphine
Sulfides
Gastrointestinal Agents
Corpus Striatum
Dopamine Antagonists
Chlorpromazine
Ammonium Compounds
Antipsychotic Agents
Nitrogen
ammonium sulfide
benzamide

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

The Interaction of Ammonium, Sulfonium, and Sulfide Analogues of Metoclopramide with the Dopamine D2 Receptor. / Harrold, Marc W.; Sriburi, Anong; Matsumoto, Kazuhisa; Miller, Duane; Farooqui, Tahira; Uretsky, Norman.

In: Journal of Medicinal Chemistry, Vol. 36, No. 21, 01.01.1993, p. 3166-3170.

Research output: Contribution to journalArticle

Harrold, Marc W. ; Sriburi, Anong ; Matsumoto, Kazuhisa ; Miller, Duane ; Farooqui, Tahira ; Uretsky, Norman. / The Interaction of Ammonium, Sulfonium, and Sulfide Analogues of Metoclopramide with the Dopamine D2 Receptor. In: Journal of Medicinal Chemistry. 1993 ; Vol. 36, No. 21. pp. 3166-3170.
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