A Double-Blind Comparison of Three Dosages of Flutroline (CP-36,584) in the Treatment of Schizophrenia

Abstract

Therapeutic and adverse effects of three dosages (1, 20 and 100 mg daily) of flutroline, a new 7-carboline with a predinical pharmacological profile similar to active neuroleptic agents, were compared in a double-blind clinical trial in 25 newly-admitted schizophrenic patients. Therapeutic effects and extrapyramidal signs were seen at the 20 and 100-mg daily dosages, but not at the 1-mg dosage. Serum prolactin levels were significantly elevated only at the 100-mg daily dosage.

Neuroleptics from the 4a,9b-cis- and 4a,9b-trans-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole series. 2

“…Compounds 6, 7, 9, and 13 are capable of potent interaction with the DA receptor as measured by their ability to displace [3H]spiroperidol from striatal homogenates, contrasting with the lack of activity of compounds 1-3 and the limited activity of compound 4 in this test. Again it will be noted that secondary amines (compound 6) or simple alkylsubstituted compounds (compounds [7][8][9] have limited activity in the in vivo screen, but the intrinsic activity of the trans tricyclic nucleus can be deduced from their relatively potent binding activities in the in vitro assay. When trans compounds 7 and 9 are compared directly with cis compounds 2 and 3, it is obvious that the trans derivatives are capable of much better interaction with the receptor.…”

“…trails-(±)-2-Benzyl-5-phenyl-2,3,4,4a,5,9b-hexahydro-l.ffpyrido [4,3-b ]indole Hydrochloride (9). To 150 mL of a stirred solution of 0.93 M borane in THF (140 mmol) at 0-5 °C was added 23.9 g (71 mmol) of 2-benzyl-5-phenyl-1,2,3,4-tetrahydropyrido- [4,[3][4][5]indole23 in 460 mL of THF.…”

Iodine-Catalyzed Cascade Formal [3 + 3] Cycloaddition Reaction of Indolyl Alcohol Derivatives with Enaminones: Constructions of Functionalized Spirodihydrocarbolines

“…Among of them, γ-carbolines have attracted special attention in organic synthesis for their versatile biological activities. Numerous γ-carboline medical agents have been designed and synthesized, many of which have shown specific effects on the human cardiovascular and nervous systems. , For example, SK5M (5-methyl-γ-carboline, IV ) showed antibovine viral diarrhea virus (BVDV) activity; Dimebon ( V ) is an antihistamine drug; Flutroline (CP-36584) ( VI ) is a novel antipsychotic drug; and compounds VII showed antagonist activities at human 5-HT 6 and H 1 receptors (Figure ) . A literature survey indicates that several strategies have been applied to synthesis of γ-carboline derivatives, such as Fischer indole synthesis, iso-Pictet–Spengler reaction of isotryptamine with aldehydes, benzyne strategy from 2-fluorophenyl imines with LDA, as well as Pd(OAc) 2 /Cu(OAc) 2 or a hypervalent iodine reagent-promoted oxidative annulation strategy .…”