(R)-(-)-[77Br]4-Bromo-2,5-dimethoxyamphetamine labels a novel 5-hydroxytryptamine binding site in brain membranes

S. J. Peroutka, A. Hamik, M. A. Harrington, A. J. Hoffman, C. A. Mathis, P. A. Pierce, S. S.H. Wang

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24 Scopus citations


(R)-(-)-[77Br]4-Bromo-2,5-dimethoxyamphetamine [(R)-(-)-[77Br]DOB] was synthesized to a high specific activity (1875 ± 50 Ci/mmol) and used to label membrane-associated recognition sites in rat brain. (R)-(-)-[77Br]DOB displayed high affinity (K(D) = 0.60 ± 0.08 nM) for a relatively low density of binding sites (B(max) = 1.2 ± 0.08 pmol/g of tissue) in rat cortical membranes as compared with [3H]ketanserin (K(D) = 0.65 ± 0.1 nM; B(max) = 6.2 ± 0.6 pmol/g of tissue). Guanine, but not adenine, nucleotides were found to inhibit specific (R)-(-)-[77Br]DOB binding. GTP (10-4 M) did not eliminate specific (R)-(-)-[77Br]DOB binding but caused a competitive inhibition of the radioligand. Drug competition studies of 5-hydroxytryptamine (5-HT) and related agents indicate that both putative agonists and antagonists display nanomolar potency for these sites. A significant correlation (p < 0.01) exists between drug potencies for (R)-(-)-[77Br]DOB-labeled sites and both 5-HT2 (r = 0.64) and 5-HT(1C) (r = 0.68) binding sites. However, the sites do not appear to be identical. Moreover, a significant correlation exists between drug potencies for (R)-(-)-[77Br]DOB-labeled sites and human hallucinogenic drug potencies (r = 0.89; p < 0.01). We conclude that (R)-(-)-[77Br]DOB labels a unique 5-HT recognition site in rat brain that does not coincide with previously described 5-HT binding site subtypes. The (R)-(-)-[77Br]DOB site does not appear to be a high affinity 'state' of the 5-HT2 receptor but may label a subset of heterogeneous 5-HT2 recognition sites.

Original languageEnglish (US)
Pages (from-to)537-542
Number of pages6
JournalMolecular Pharmacology
Issue number4
StatePublished - 1988
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology


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