Systematic Studies with Amoxapine, a New Antidepressant

Abstract

Amoxapine, a tricyclic dibenzoxazepine is an antidepressant which in the dosage range of 150-300 mg/day is notable for its rapid onset of action. Because of the rather long, approximately 30-hour, half-life of 8-hydroxyamoxapine, the active metabolite of amoxapine, the possibility was raised that amoxapine therapy may be carried out with single daily dosages. Such a dosage schedule may improve compliance and, if appropriately timed, decrease perception of some of the unwanted effects of the drug. To test the hypothesis that there may be no disadvantages and perhaps even advantages of a oncea- day regimen as compared to a divided dosage schedule, a 6-week double-blind clinical trial was carried out in 35 hospitalized patients with major (18 patients) and minor (17 patients) depressive disorders. While no statistically significant difference was found in overall therapeutic and adverse effects between the groups treated with single or divided daily doses, onset of therapeutic effect appeared a bit faster in the group treated with single daily doses. Of particular relevance for drugs which can be given in single daily doses is their effect on psychomotor performance tests. In view of the findings that a once-a-day dosage regimen with amoxapine may have advantages over divided daily doses, a second study was carried out in which the effects of amoxapine (50 and 100 mg) were compared to an inactive placebo and amitriptyline (50 mg) with and without ethanol in 8 normal male volunteers. The study was double-blind and followed a latin square design. Since the effects of amoxapine on motor reflex, visual-motor coordination and depth perception did not differ significantly from placebo, the results suggest that the effects of amoxapine on the performances measured are clinically insignificant. No significant interaction with ethanol was noted.

Fluorofunctionalization of C═C Bonds with Selectfluor: Synthesis of β-Fluoropiperazines through a Substrate-Guided Reactivity Switch

“…For example, we demonstrated this approach on four alkenes and obtained the reduced products in good yields. We anticipate that a one-pot strategy to synthesize fluoropiperazines will be of great use to medicinal chemists, given the ubiquity of both piperazines and fluorine in pharmaceuticals . The fluoropiperazine products were transformed into Cbz derivatives to facilitate chromatography (compounds 14 – 17 ); however, they could also be isolated as the free secondary amines or instead alkylated or acylated with any appropriate electrophile.…”

Identification of a Novel Drug Lead That Inhibits HCV Infection and Cell-to-Cell Transmission by Targeting the HCV E2 Glycoprotein

“…Numerous structural analogs of 281816 have been tested and shown to be effective in treating a wide variety of neurological diseases (schizophrenia [97], [98], Parkinson and dementia-related psychoses [99], [100]), bipolar disorders [101], [102], and depression [103], [104]. While we have not found experimental studies that report the membrane permeability of 281816, the logP (log of octanol/water partition coefficient) has been calculated to be 4.14, which indicates the compound is likely to exhibit good membrane permeability.…”

Polyketopiperazines: triketopiperazines, tetraketopiperazines synthesis, reactions, bioactivities and applications

“…Most importantly, piperazine is an essential heterocyclic motif in many biologically active compounds with various pharmacological activities. [19][20][21][22][23][24][25][26][27] For example, clozapine 1 is strongly sedative and has muscle-relaxant properties, amoxapine 2 has antidepressant activity, trimetazidine 3 is an antischemic agent and cyclizine 4 is used to treat nausea and vomiting 28,29 (Figure 1). Structurally, piperazine has a six-membered saturated ring with two nitrogen atoms at 1-and 4-positions.…”