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M L De Ceballos - One of the best experts on this subject based on the ideXlab platform.

  • Butyrophenone analogues: Synthesis of 2-methyl-3-ethyl-5-aminoethyl-4,5,6,7-tetrahydroindol-4-ones, and their affinities for d1, d2 and 5-ht2a receptors
    'Elsevier BV', 2013
    Co-Authors: Raviña Enrique, Masaguer, Cristian F., Cid J., Fontenla, José Ángel, Ferreiro T. G., Cadavid M., Loza-garcía Isabel, M L De Ceballos
    Abstract:

    Starting from 2-methyl-3-ethyl-1H-4,5,6,7-tetrahydroindol-4-one 3 we have prepared 2-methyl-3-ethyl-5-morpholinoethyl-1H-4, 5,6,7-tetrahydroindol-4-one, (1) and 2-methyl-3-ethyl-5-(4-o-methoxyphenyl-1-piperazinoethyl)-1H-4,5,6,7-tetr ahydroindol-4-one (2) as butyrophenone analogues of the neuroleptic Molindone. The affinities of these compounds for D1 and D2 dopamine and 5-HT2A serotonin receptors were evaluated in vitro. The affinity of 1 for D2 receptors is less than that of Molindone (pKi's 6.23 and 7.48 respectively) and that of 2 similar (pKi 7.55). Both compounds bind to 5-HT2A receptors, the affinity of 2 being significantly greater than that of Molindone (pKi's of 7.04 and 5.85, and pA2′s of 7.50 and 6.18, respectively). © 1995 Elsevier Science Ltd.Peer Reviewe

  • butyrophenone analogues synthesis of 2 methyl 3 ethyl 5 aminoethyl 4 5 6 7 tetrahydroindol 4 ones and their affinities for d1 d2 and 5 ht2a receptors
    Bioorganic & Medicinal Chemistry Letters, 1995
    Co-Authors: C F Masaguer, Jose Angel Cid, Isabel Casariego, J A Fontenla, T G Ferreiro, Maria Isabel Cadavid, Maria Isabel Loza, M L De Ceballos
    Abstract:

    Starting from 2-methyl-3-ethyl-1H-4,5,6,7-tetrahydroindol-4-one 3 we have prepared 2-methyl-3-ethyl-5-morpholinoethyl-1H-4, 5,6,7-tetrahydroindol-4-one, (1) and 2-methyl-3-ethyl-5-(4-o-methoxyphenyl-1-piperazinoethyl)-1H-4,5,6,7-tetrahydroindol-4-one (2) as butyrophenone analogues of the neuroleptic Molindone. The affinities of these compounds for D1 and D2 dopamine and 5-HT2A serotonin receptors were evaluated in vitro. The affinity of 1 for D2 receptors is less than that of Molindone (pKi's 6.23 and 7.48 respectively) and that of 2 similar (pKi 7.55). Both compounds bind to 5-HT2A receptors, the affinity of 2 being significantly greater than that of Molindone (pKi's of 7.04 and 5.85, and pA2′s of 7.50 and 6.18, respectively).

C F Masaguer - One of the best experts on this subject based on the ideXlab platform.

  • butyrophenone analogues synthesis of 2 methyl 3 ethyl 5 aminoethyl 4 5 6 7 tetrahydroindol 4 ones and their affinities for d1 d2 and 5 ht2a receptors
    Bioorganic & Medicinal Chemistry Letters, 1995
    Co-Authors: C F Masaguer, Jose Angel Cid, Isabel Casariego, J A Fontenla, T G Ferreiro, Maria Isabel Cadavid, Maria Isabel Loza, M L De Ceballos
    Abstract:

    Starting from 2-methyl-3-ethyl-1H-4,5,6,7-tetrahydroindol-4-one 3 we have prepared 2-methyl-3-ethyl-5-morpholinoethyl-1H-4, 5,6,7-tetrahydroindol-4-one, (1) and 2-methyl-3-ethyl-5-(4-o-methoxyphenyl-1-piperazinoethyl)-1H-4,5,6,7-tetrahydroindol-4-one (2) as butyrophenone analogues of the neuroleptic Molindone. The affinities of these compounds for D1 and D2 dopamine and 5-HT2A serotonin receptors were evaluated in vitro. The affinity of 1 for D2 receptors is less than that of Molindone (pKi's 6.23 and 7.48 respectively) and that of 2 similar (pKi 7.55). Both compounds bind to 5-HT2A receptors, the affinity of 2 being significantly greater than that of Molindone (pKi's of 7.04 and 5.85, and pA2′s of 7.50 and 6.18, respectively).

Ann E Maloney - One of the best experts on this subject based on the ideXlab platform.

  • Olanzapine approved for the acute treatment of schizophrenia or manic/mixed episodes associated with bipolar I disorder in adolescent patients
    Dove Medical Press, 2010
    Co-Authors: Ann E Maloney, Linmarie Sikich
    Abstract:

    Ann E Maloney1,2, Linmarie Sikich31Maine Medical Center Research Institute, Scarborough, ME, USA; 2Department of Psychiatry, Tufts University School of Medicine, Boston, MA, USA; 3Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USABackground: Severe and persistent mental illnesses in children and adolescents, such as early-onset schizophrenia spectrum (EOSS) disorders and pediatric bipolar disorder (pedBP), are increasingly recognized. Few treatments have demonstrated efficacy in rigorous clinical trials. Enduring response to current medications appears limited. Recently, olanzapine was approved for the treatment of adolescents with schizophrenia or acute manic/mixed episodes in pedBP.Methods: PubMed searches were conducted for olanzapine combined with pharmacology, schizophrenia, or bipolar disorder. Searches related to schizophrenia and bipolar disorder were limited to children and adolescents. The bibliographies of the retrieved articles were hand-checked for additional relevant studies. The epidemiology, phenomenology, and treatment of EOSS and pedBP, and olanzapine’s pharmacology are reviewed. Studies of olanzapine treatment in youth with EOSS and pedBP are examined.Results: Olanzapine is efficacious for EOSS and pedBP. However, olanzapine is not more efficacious than risperidone, Molindone, or haloperidol in EOSS and is less efficacious than clozapine in treatment-resistant EOSS. No comparative trials have been done in pedBP. Olanzapine is associated with weight gain, dyslipidemia, and transaminase elevations in youth. Extrapyramidal symptoms, neuroleptic malignant syndrome, and blood dyscrasias have also been reported but appear rare.Conclusions: The authors conclude that olanzapine should be considered a second-line agent in EOSS and pedBP due to its risks for significant weight gain and lipid dysregulation. Awareness of the consistent weight and metabolic changes observed in olanzapine-treated youth focused attention on the potential long-term risks of atypical antipsychotics in youth.Keywords: early-onset schizophrenia, pediatric bipolar disorder, antipsychoti

  • double blind comparison of first and second generation antipsychotics in early onset schizophrenia and schizo affective disorder findings from the treatment of early onset schizophrenia spectrum disorders teoss study
    American Journal of Psychiatry, 2008
    Co-Authors: Linmarie Sikich, Jean A Frazier, Jon Mcclellan, Robert L Findling, Benedetto Vitiello, Louise Ritz, Denisse Ambler, Madeline Puglia, Ann E Maloney, Emily S Michael
    Abstract:

    Objective: Atypical (second-generation) antipsychotics are considered standard treatment for children and adolescents with early-onset schizophrenia and schizoaffective disorder. However, the superiority of second-generation antipsychotics over first-generation antipsychotics has not been demonstrated. This study compared the efficacy and safety of two second-generation antipsychotics (olanzapine and risperidone) with a first-generation antipsychotic (Molindone) in the treatment of early-onset schizophrenia and schizoaffective disorder. Method: This double-blind multisite trial randomly assigned pediatric patients with early-onset schizophrenia and schizoaffective disorder to treatment with either olanzapine (2.5–20 mg/day), risperidone (0.5–6 mg/day), or Molindone (10–140 mg/day, plus 1 mg/day of benztropine) for 8 weeks. The primary outcome was response to treatment, defined as a Clinical Global Impression (CGI) improvement score of 1 or 2 and ≥20% reduction in Positive and Negative Syndrome Scale (PANS...

  • treatment of early onset schizophrenia spectrum disorders teoss rationale design and methods
    Journal of the American Academy of Child and Adolescent Psychiatry, 2007
    Co-Authors: Jon Mcclellan, Linmarie Sikich, Jean A Frazier, Robert L Findling, Benedetto Vitiello, Denisse Ambler, Stefanie A Hlastala, Emily Williams, Tyehimba Huntharrison, Ann E Maloney
    Abstract:

    ABSTRACT Objective: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and Molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early Onset Schizophrenia Spectrum Disorders Study are described. Method: Using a randomized, double-blind, parallel-group design at four sites, youths with EOSS (ages 8-19 years) were assigned to an 8-week acute trial of risperidone (0.5-6.0 mg/day), olanzapine (2.5-20 mg/day), or Molindone (10-140 mg/day). Responders continued double-blind treatment for 44 weeks. The primary outcome measure was responder status at 8 weeks, defined by a 20% reduction in baseline Positive and Negative Symptom Scale scores plus ratings of significant improvement on the Clinical Global Impressions. Secondary outcome measures included assessments of psychopathology, functional impairment, quality of life, and medication safety. An intent-to-treat analytic plan was used. Results: From February 2002 to May 2006, 476 youths were screened, 173 were further evaluated, and 119 were randomized. Several significant study modifications were required to address safety, the use of adjunctive medications, and the termination of the olanzapine treatment arm due to weight gain. Conclusions: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study will inform clinical practice regarding the use of antipsychotic medications for youths with early-onset schizophrenia spectrum disorders. Important safety concerns emerged during the study, including higher than anticipated rates of suicidality and problems tapering thymoleptic agents before randomization.

Linmarie Sikich - One of the best experts on this subject based on the ideXlab platform.

  • Olanzapine approved for the acute treatment of schizophrenia or manic/mixed episodes associated with bipolar I disorder in adolescent patients
    Dove Medical Press, 2010
    Co-Authors: Ann E Maloney, Linmarie Sikich
    Abstract:

    Ann E Maloney1,2, Linmarie Sikich31Maine Medical Center Research Institute, Scarborough, ME, USA; 2Department of Psychiatry, Tufts University School of Medicine, Boston, MA, USA; 3Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USABackground: Severe and persistent mental illnesses in children and adolescents, such as early-onset schizophrenia spectrum (EOSS) disorders and pediatric bipolar disorder (pedBP), are increasingly recognized. Few treatments have demonstrated efficacy in rigorous clinical trials. Enduring response to current medications appears limited. Recently, olanzapine was approved for the treatment of adolescents with schizophrenia or acute manic/mixed episodes in pedBP.Methods: PubMed searches were conducted for olanzapine combined with pharmacology, schizophrenia, or bipolar disorder. Searches related to schizophrenia and bipolar disorder were limited to children and adolescents. The bibliographies of the retrieved articles were hand-checked for additional relevant studies. The epidemiology, phenomenology, and treatment of EOSS and pedBP, and olanzapine’s pharmacology are reviewed. Studies of olanzapine treatment in youth with EOSS and pedBP are examined.Results: Olanzapine is efficacious for EOSS and pedBP. However, olanzapine is not more efficacious than risperidone, Molindone, or haloperidol in EOSS and is less efficacious than clozapine in treatment-resistant EOSS. No comparative trials have been done in pedBP. Olanzapine is associated with weight gain, dyslipidemia, and transaminase elevations in youth. Extrapyramidal symptoms, neuroleptic malignant syndrome, and blood dyscrasias have also been reported but appear rare.Conclusions: The authors conclude that olanzapine should be considered a second-line agent in EOSS and pedBP due to its risks for significant weight gain and lipid dysregulation. Awareness of the consistent weight and metabolic changes observed in olanzapine-treated youth focused attention on the potential long-term risks of atypical antipsychotics in youth.Keywords: early-onset schizophrenia, pediatric bipolar disorder, antipsychoti

  • double blind comparison of first and second generation antipsychotics in early onset schizophrenia and schizo affective disorder findings from the treatment of early onset schizophrenia spectrum disorders teoss study
    American Journal of Psychiatry, 2008
    Co-Authors: Linmarie Sikich, Jean A Frazier, Jon Mcclellan, Robert L Findling, Benedetto Vitiello, Louise Ritz, Denisse Ambler, Madeline Puglia, Ann E Maloney, Emily S Michael
    Abstract:

    Objective: Atypical (second-generation) antipsychotics are considered standard treatment for children and adolescents with early-onset schizophrenia and schizoaffective disorder. However, the superiority of second-generation antipsychotics over first-generation antipsychotics has not been demonstrated. This study compared the efficacy and safety of two second-generation antipsychotics (olanzapine and risperidone) with a first-generation antipsychotic (Molindone) in the treatment of early-onset schizophrenia and schizoaffective disorder. Method: This double-blind multisite trial randomly assigned pediatric patients with early-onset schizophrenia and schizoaffective disorder to treatment with either olanzapine (2.5–20 mg/day), risperidone (0.5–6 mg/day), or Molindone (10–140 mg/day, plus 1 mg/day of benztropine) for 8 weeks. The primary outcome was response to treatment, defined as a Clinical Global Impression (CGI) improvement score of 1 or 2 and ≥20% reduction in Positive and Negative Syndrome Scale (PANS...

  • treatment of early onset schizophrenia spectrum disorders teoss rationale design and methods
    Journal of the American Academy of Child and Adolescent Psychiatry, 2007
    Co-Authors: Jon Mcclellan, Linmarie Sikich, Jean A Frazier, Robert L Findling, Benedetto Vitiello, Denisse Ambler, Stefanie A Hlastala, Emily Williams, Tyehimba Huntharrison, Ann E Maloney
    Abstract:

    ABSTRACT Objective: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and Molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early Onset Schizophrenia Spectrum Disorders Study are described. Method: Using a randomized, double-blind, parallel-group design at four sites, youths with EOSS (ages 8-19 years) were assigned to an 8-week acute trial of risperidone (0.5-6.0 mg/day), olanzapine (2.5-20 mg/day), or Molindone (10-140 mg/day). Responders continued double-blind treatment for 44 weeks. The primary outcome measure was responder status at 8 weeks, defined by a 20% reduction in baseline Positive and Negative Symptom Scale scores plus ratings of significant improvement on the Clinical Global Impressions. Secondary outcome measures included assessments of psychopathology, functional impairment, quality of life, and medication safety. An intent-to-treat analytic plan was used. Results: From February 2002 to May 2006, 476 youths were screened, 173 were further evaluated, and 119 were randomized. Several significant study modifications were required to address safety, the use of adjunctive medications, and the termination of the olanzapine treatment arm due to weight gain. Conclusions: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study will inform clinical practice regarding the use of antipsychotic medications for youths with early-onset schizophrenia spectrum disorders. Important safety concerns emerged during the study, including higher than anticipated rates of suicidality and problems tapering thymoleptic agents before randomization.

J A Fontenla - One of the best experts on this subject based on the ideXlab platform.

  • butyrophenone analogues synthesis of 2 methyl 3 ethyl 5 aminoethyl 4 5 6 7 tetrahydroindol 4 ones and their affinities for d1 d2 and 5 ht2a receptors
    Bioorganic & Medicinal Chemistry Letters, 1995
    Co-Authors: C F Masaguer, Jose Angel Cid, Isabel Casariego, J A Fontenla, T G Ferreiro, Maria Isabel Cadavid, Maria Isabel Loza, M L De Ceballos
    Abstract:

    Starting from 2-methyl-3-ethyl-1H-4,5,6,7-tetrahydroindol-4-one 3 we have prepared 2-methyl-3-ethyl-5-morpholinoethyl-1H-4, 5,6,7-tetrahydroindol-4-one, (1) and 2-methyl-3-ethyl-5-(4-o-methoxyphenyl-1-piperazinoethyl)-1H-4,5,6,7-tetrahydroindol-4-one (2) as butyrophenone analogues of the neuroleptic Molindone. The affinities of these compounds for D1 and D2 dopamine and 5-HT2A serotonin receptors were evaluated in vitro. The affinity of 1 for D2 receptors is less than that of Molindone (pKi's 6.23 and 7.48 respectively) and that of 2 similar (pKi 7.55). Both compounds bind to 5-HT2A receptors, the affinity of 2 being significantly greater than that of Molindone (pKi's of 7.04 and 5.85, and pA2′s of 7.50 and 6.18, respectively).