Synthesis and Pharmacological Evaluation of Sulfonium Analogues of Dopamine

Nonclassical Dopamine Agonists

Karen Anderson, Alice Kuruvilla, Norman Uretsky, Duane Miller

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

In order to test whether the nitrogen/ammonium moiety in the dopamine molecule is required for dopaminergic activity, we have synthesized two sulfonium analogues of dopamine and tested them for biological activity in an in vivo and in an in vitro system. These analogues have provided a means of investigating (1) the ability of the sulfonium function to serve as a bioisostere for the dopamine amino group and (2) whether charged molecules have the ability to bind to dopamine receptors. Both sulfonium analogues, 1 and 2, as well as dopamine, when injected directly into the striatum of rats, previously lesioned unilaterally with 6-hydroxydopamine (6-OHDA), produced circling behavior. The potency of the sulfonium analogues was approximately one-tenth that of dopamine. The effects of all three compounds on circling were inhibited by the dopamine antagonist haloperidol. In addition, both sulfonium analogues inhibited the high affinity binding of radiolabeled dopamine to a crude membrane fraction prepared from the striatum. This study suggests that the nitrogen atom found in the dopamine molecule is not essential for dopaminergic activity, since the nitrogen can be replaced by a sulfonium functional group for this activity.

Original languageEnglish (US)
Pages (from-to)683-687
Number of pages5
JournalJournal of Medicinal Chemistry
Volume24
Issue number6
DOIs
StatePublished - Jan 1 1981
Externally publishedYes

Fingerprint

Dopamine Agonists
Dopamine
Pharmacology
Aptitude
Nitrogen
Oxidopamine
Dopamine Antagonists
Dopamine Receptors
Haloperidol
Ammonium Compounds
Membranes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Synthesis and Pharmacological Evaluation of Sulfonium Analogues of Dopamine : Nonclassical Dopamine Agonists. / Anderson, Karen; Kuruvilla, Alice; Uretsky, Norman; Miller, Duane.

In: Journal of Medicinal Chemistry, Vol. 24, No. 6, 01.01.1981, p. 683-687.

Research output: Contribution to journalArticle

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