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Stephen L Buchwald - One of the best experts on this subject based on the ideXlab platform.

  • concise palladium catalyzed synthesis of dibenzodiazepines and structural analogues
    Journal of the American Chemical Society, 2011
    Co-Authors: Dmitry Tsvelikhovsky, Stephen L Buchwald
    Abstract:

    A general and highly efficient protocol for the synthesis of dibenzodiazepines and their structural analogues is reported. In the presence of catalytic quantities of palladium, readily accessible precursors are cross-coupled with ammonia and then spontaneously undergo an intramolecular condensation to form the corresponding dibenzodiazepines in one step. This new strategy is applicable to the construction of a wide variety of dibenzooxazepines and other structurally related heterocycles.

Dmitry Tsvelikhovsky - One of the best experts on this subject based on the ideXlab platform.

  • concise palladium catalyzed synthesis of dibenzodiazepines and structural analogues
    Journal of the American Chemical Society, 2011
    Co-Authors: Dmitry Tsvelikhovsky, Stephen L Buchwald
    Abstract:

    A general and highly efficient protocol for the synthesis of dibenzodiazepines and their structural analogues is reported. In the presence of catalytic quantities of palladium, readily accessible precursors are cross-coupled with ammonia and then spontaneously undergo an intramolecular condensation to form the corresponding dibenzodiazepines in one step. This new strategy is applicable to the construction of a wide variety of dibenzooxazepines and other structurally related heterocycles.

Shitij Kapur - One of the best experts on this subject based on the ideXlab platform.

  • amoxapine shows an antipsychotic effect but worsens motor function in patients with parkinson s disease and psychosis
    Clinical Neuropharmacology, 2001
    Co-Authors: Shitij Kapur, Anthony E Lang
    Abstract:

    Amoxapine, a dibenzoxazepine antidepressant, has been suggested to have atypical antipsychotic properties. We tested it to control psychosis in three patients with Parkinson's disease (PD). Two patients had significant improvement in hallucinations, whereas the third could not tolerate the drug for a sufficient period. All three patients experienced a decline in motor function; two also had concomitant reduction in dyskinesias. Therefore, although we found some support for amoxapine having antipsychotic properties, this drug seems to carry a risk of worsening motor function in patients with PD.

  • antipsychoticlike effects of amoxapine without catalepsy using the prepulse inhibition of the acoustic startle reflex test in rats
    Biological Psychiatry, 2000
    Co-Authors: Marielouise G Wadenberg, Shitij Kapur, Terrence L Sills, Paul J Fletcher
    Abstract:

    Abstract Background: The dibenzoxazepine amoxapine was introduced as an antidepressant but has shown antipsychoticlike activity in a number of animal screening tests. A recent positron emission tomography study showed a 5-HT 2 /D 2 receptor occupancy profile of amoxapine that is very similar to that of established atypical antipsychotics. Schizophrenics display deficits in sensory gating mechanisms, such as prepulse inhibition (PPI) of the acoustic startle reflex. A similar deficit can be produced by dopamine (DA) and by 5-HT 2A/C receptor agonists in rats. Antipsychotic compounds reverse this effect. Methods: Effects of amoxapine on apomorphine- or 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced disruption of PPI were studied in adult male Sprague-Dawley rats. The extrapyramidal side effect (EPS) liability of amoxapine was assessed using the inclined grid catalepsy (CAT) test. Statistical analyses were performed by analysis of variance (ANOVA) for fully repeated measures (PPI) and by the Kruskal–Wallis one-way ANOVA by ranks (CAT). Results: Apomorphine (0.5 mg/kg) produced a significant reduction in PPI compared with the case of rats in the saline control group. Pretreatment with amoxapine (10 mg/kg) significantly attenuated the apomorphine-induced disruption of PPI. DOI (0.5 mg/kg) significantly reduced PPI compared with saline controls. Pretreatment with amoxapine (5 or 10 mg/kg) produced a significant attenuation of the DOI-induced disruption of PPI. Amoxapine by itself did not alter PPI. Amoxapine (5 or 10 mg/kg) did not produce CAT. Conclusions: The DA D 2 /5-HT 2 receptor antagonist amoxapine produced an antipsychoticlike reversal of both apomorphine- and DOI-induced disruption of PPI. Furthermore, the same doses of amoxapine that reversed disruption of PPI did not produce CAT. The results confirm and lend further support to the results of previous studies on amoxapine, suggesting that amoxapine might possess antipsychotic activity with little propensity for producing EPS.

  • pet evidence that loxapine is an equipotent blocker of 5 ht2 and d2 receptors implications for the therapeutics of schizophrenia
    American Journal of Psychiatry, 1997
    Co-Authors: Shitij Kapur, Gordon Mckay, Gary Remington, Robert B Zipursky, C Jones, Sylvain Houle
    Abstract:

    OBJECTIVE: Loxapine, a dibenzoxazepine antipsychotic, is closely related to clozapine and shares clozapine's high affinity for binding to serotonin 5-HT2 and dopamine D4 receptors. The purpose of this study was to document loxapine's 5-HT2 and D2 receptor occupancy in vivo in patients with psychoses. METHOD: Ten patients who were taking loxapine (10–100 mg/day) had their D2 and 5-HT2 receptors assessed by means of positron emission tomography with [11C]raclopride and [18F]setoperone, respectively. RESULTS: The D2 receptor occupancy ranged from 43% to 90% 5-HT2 occupancy varied from 27% to near saturation. Statistical comparison of the results showed that loxapine was equipotent in blocking 5-HT2 and D2 receptors. CONCLUSIONS: Loxapine differs from typical neuroleptics in demonstrating a high degree of 5-HT2 receptor occupancy. However, it is not “atypical” like clozapine and risperidone, since its 5-HT2 occupancy is not higher than its D2 occupancy. The results demonstrate that a high level of 5-HT2 occup...

Fereshteh Faraji - One of the best experts on this subject based on the ideXlab platform.

Pincemail Joël - One of the best experts on this subject based on the ideXlab platform.

  • Peroxidase-Catalysed Oxidation of Different Dibenzazepine Derivatives
    'Wiley', 1995
    Co-Authors: Liégeois Jean-françois, Rogister F., Delarge J., Pincemail Joël
    Abstract:

    peer reviewedaudience: researcher, professional, studentAccording to a recent hypothesis suggesting the potential role of free radical formation in the clozapine-induced agranulocytosis, we have evaluated the susceptibility to the peroxidase-mediated oxidation of different dibenzazepine analogues. On the one hand, compounds with an arylamine group such as clozapine or isoclozapine present a high reactivity in the horseradish peroxidase or myeloperoxidase systems and, on the other hand, fluperlapine, though known to induce agranulocytosis, and other dibenzothiazepine and dibenzoxazepine derivatives appear insensitive to oxidation. Consequently, among tricyclic derivatives, the way of diaryloxa- and diarylthiazepine compounds could be an alternative for the development of safer drugs such as antipsychotics

  • Peroxidase-Catalysed Oxidation of Different Dibenzazepine Derivatives
    1995
    Co-Authors: Liégeois Jean-françois, Rogister F., Delarge J., Pincemail Joël
    Abstract:

    According to a recent hypothesis suggesting the potential role of free radical formation in the clozapine-induced agranulocytosis, we have evaluated the susceptibility to the peroxidase-mediated oxidation of different dibenzazepine analogues. On the one hand, compounds with an arylamine group such as clozapine or isoclozapine present a high reactivity in the horseradish peroxidase or myeloperoxidase systems and, on the other hand, fluperlapine, though known to induce agranulocytosis, and other dibenzothiazepine and dibenzoxazepine derivatives appear insensitive to oxidation. Consequently, among tricyclic derivatives, the way of diaryloxa- and diarylthiazepine compounds could be an alternative for the development of safer drugs such as antipsychotics.Peer reviewe