title: Evaluation of isotryptamine derivatives at 5-HT(2) serotonin receptors.
abstract: On the basis that meta-chlorophenylpiperazine (mCPP; 1) is a nonselective 5-HT(2C) agonist, that benz-fused tryptamines (e.g., 5) display enhanced 5-HT(2) affinity, and that certain isotryptamines 3 reportedly bind with enhanced affinity and selectivity at 5-HT(2C) receptors, we prepared and examined a series of isotryptamine-related analogues as potentially selective 5-HT(2C) agonists. None of the compounds displayed selectivity for 5-HT(2C) versus 5-HT(2A) receptors. Detailed re-examination of a compound previously reported to display 100-fold 5-HT(2C) selectivity [i.e., S(+)-5,6-difluoro-alpha-methylisotryptamine] revealed that its selectivity versus 5-HT(2A) receptors was, at best, only 10-fold.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Chang-Fong
authors.forename: James
authors.initials: J
authors.lastname: Addo
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Dukat
authors.forename: Carol
authors.initials: C
authors.lastname: Smith
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Mitchell
authors.forename: Katharine
authors.initials: K
authors.lastname: Herrick-Davis
authors.forename: Milt
authors.initials: M
authors.lastname: Teitler
authors.forename: Richard A
authors.initials: RA
authors.lastname: Glennon
mesh_terms: D004353:Drug Evaluation, Preclinical; D006801:Humans; D011985:Receptors, Serotonin / Q000187:drug effects*; D014363:Tryptamines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D011985:Receptors, Serotonin; D014363:Tryptamines; C030820:tryptamine