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

  • Amoxapine as an antipsychotic: comparative study versus haloperidol.
    Journal of clinical psychopharmacology, 2007
    Co-Authors: Imran B Chaudhry, Nusrat Husain, Salahuddin Khan, Sareer Badshah, Bill Deakin, Shitij Kapur
    Abstract:

    It has been proposed that the lack of extrapyramidal side effects of atypical antipsychotic drugs is caused by their fast dissociation or low affinity for the D2 receptor or their concomitant high affinity for other receptors, for example, 5HT2 and D4. We noted that Amoxapine, an established antidepressant, has affinity for 5HT2 and D2 receptors, and its effects in preclinical model are very similar to atypical antipsychotics. The objective of this study was to examine the antipsychotic effect and side effect profile of Amoxapine versus haloperidol in a double-blind study for 6 weeks in patients with schizophrenia. A total of 54 patients with schizophrenia were titrated to the starting dose of 150 mg/d of Amoxapine or 5 mg/d of haloperidol within 3 days. Clinical efficacy and side effects were monitored at baseline, and Weeks 2, 4, and 6.Forty-one patients completed 5 weeks, and 36 patients completed the 6 weeks of follow-up. Both treatment groups showed significant improvement in Positive and Negative Syndrome Scale positive (30%) and total scores (20%), without significant differences between the groups. In addition, in the Amoxapine group, significant improvement was seen in the negative symptoms and the Clinical Global Impression. No significant changes were seen on Calgary Depression Scale for Schizophrenia, side effect checklists, and prolactin levels in both groups. The results suggest that Amoxapine may be as effective an antipsychotic as haloperidol as predicted by its affinity for D2 and 5HT2 receptors, supporting earlier studies. However, it did not prove to have fewer extrapyramidal side effects than haloperidol, possibly because the baseline scores were very low.

  • Amoxapine as an Atypical Antipsychotic: A Comparative Study Vs Risperidone
    Neuropsychopharmacology, 2005
    Co-Authors: Rogelio Apiquian, Ana Fresan, Rosa-elena Ulloa, Camilo De La Fuente-sandoval, Miguel Herrera-estrella, Alejandra Vazquez, Humberto Nicolini, Shitij Kapur
    Abstract:

    Amoxapine is marketed as an antidepressant. However, its invitro profile, receptor occupancy and preclinical effects are very similar to atypical antipsychotics. Amoxapine has also shown efficacy as an atypical antipsychotic in open trials. The objective of this study was to compare the antipsychotic and side effect profile of Amoxapine and risperidone in a randomised assignment, standardized dosing, double-blind trial of acutely psychotic patients with schizophrenia. A total of 48 schizophrenic patients were enrolled and randomized in a double-blind 6-week trial to receive either risperidone (up to 5 mg/day) or Amoxapine (up to 250 mg/day). Positive, negative, affective symptoms and motor side effects were measured using standardized weekly assessments. Prolactin levels were also determined at baseline and at the end of the study. A total of 39 patients (Amoxapine, n =22; risperidone, n =21) completed the trial. Both pharmacological treatments, Amoxapine 228.0 mg/day (SD=34.6) and risperidone 4.5 mg/day (SD=0.7), showed equivalent improvement in positive, negative, and depressive symptoms. Amoxapine was associated with less EPS and less prolactin elevation than risperidone. These data support previous reports about the efficacy of Amoxapine as an atypical antipsychotic. Since Amoxapine is off-patent, it may be a valuable low-cost alternative to new atypical antipsychotics, particularly in low-income countries where the majority of the patients are still treated with typical antipsychotics.

  • Amoxapine shows atypical antipsychotic effects in patients with schizophrenia results from a prospective open label study
    Schizophrenia Research, 2003
    Co-Authors: Rogelio Apiquian, Ana Fresan, Humberto Nicolini, Elena Ulloa, Cristina Loyzaga, Shitij Kapur
    Abstract:

    Objective: Amoxapine is marketed as an antidepressant. However, its receptor occupancy, in vitro and in vivo, and its effects in pre-clinical models are very similar to atypical antipsychotics. To examine if this leads to an atypical antipsychotic effect in the clinical context, the authors examined the antipsychotic and side-effect profile of Amoxapine in acutely psychotic patients with schizophrenia. Methods: Seventeen patients were enrolled and 15 completed a prospective open-label 6-week study of Amoxapine starting with a fixed-starting dose (150 mg/h) with standardized titration up to 250 mg/h, if required. Positive, negative, affective symptoms and side-effects were monitored using standardized weekly assessments. Results: Amoxapine (median final dose 210 mg/h) was well-tolerated and showed significant improvement in positive and negative symptoms (both p<0.001), with a trend towards improvement in mood symptoms and no treatment-emergent extrapyramidal side-effects, akathisia or weight gain. Prolactin elevation was observed. Conclusion: These clinical data lend support to the pre-clinical suggestions that Amoxapine may be an atypical antipsychotic. Given its lack of weight gain and that it is considerably less expensive than current options, Amoxapine could be a valuable alternative for some patients. These considerations strongly call for more systematic, double-blind studies of Amoxapine as an atypical antipsychotic.

  • Amoxapine shows atypical antipsychotic effects in patients with schizophrenia: results from a prospective open-label study.
    Schizophrenia research, 2003
    Co-Authors: Rogelio Apiquian, Ana Fresan, Humberto Nicolini, Elena Ulloa, Cristina Loyzaga, Shitij Kapur
    Abstract:

    Objective: Amoxapine is marketed as an antidepressant. However, its receptor occupancy, in vitro and in vivo, and its effects in pre-clinical models are very similar to atypical antipsychotics. To examine if this leads to an atypical antipsychotic effect in the clinical context, the authors examined the antipsychotic and side-effect profile of Amoxapine in acutely psychotic patients with schizophrenia. Methods: Seventeen patients were enrolled and 15 completed a prospective open-label 6-week study of Amoxapine starting with a fixed-starting dose (150 mg/h) with standardized titration up to 250 mg/h, if required. Positive, negative, affective symptoms and side-effects were monitored using standardized weekly assessments. Results: Amoxapine (median final dose 210 mg/h) was well-tolerated and showed significant improvement in positive and negative symptoms (both p

  • 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, Terrence L Sills, Paul J Fletcher, Shitij Kapur
    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.

Gang Pei - One of the best experts on this subject based on the ideXlab platform.

  • a tricyclic antidepressant Amoxapine reduces amyloid β generation through multiple serotonin receptor 6 mediated targets
    Scientific Reports, 2017
    Co-Authors: Qinying Wang, Ying Wang, Jian Zhao, Gang Pei
    Abstract:

    Alzheimer's disease (AD) is a major and devastating neurodegenerative disease, and the amyloid-β (Aβ) hypothesis is still the central theory for AD pathogenesis. Meanwhile, another major mental illness, depression, is one of the risk factors for AD. From a high-throughput screening (HTS), Amoxapine, a typical secondary amine tricyclic antidepressant (TCA), was identified to reduce Aβ production. A follow-up investigation on antidepressants showed that most of the TCAs harbour similar activity. Previous studies have indicated that TCAs improve cognitive function in AD mouse models as well as in preliminary clinical data; however, the underlying mechanism is controversial, and the effect on Aβ is elusive. Thus, we developed a secondary screening to determine the molecular target of Amoxapine, and serotonin receptor 6 (HTR6) was identified. Knockdown of HTR6 reduced the Amoxapine's effect, while the HTR6 antagonist SB258585 mimicked the activity of Amoxapine. Further mechanistic study showed that Amoxapine and SB258585 reduced Aβ generation through multiple HTR6-mediated targets, including β-arrestin2 and CDK5. Taken together, our study suggests that Amoxapine, though no longer a first-line drug for the treatment of depression, may be beneficial for AD and further structural modification of TCAs may lead to desirable therapeutic agents to treat both AD and depression.

Paul J Fletcher - One of the best experts on this subject based on the ideXlab platform.

  • 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, Terrence L Sills, Paul J Fletcher, Shitij Kapur
    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.

  • 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, Terrence L Sills, Paul J Fletcher, Shitij Kapur
    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.

Marielouise G Wadenberg - One of the best experts on this subject based on the ideXlab platform.

  • 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, Terrence L Sills, Paul J Fletcher, Shitij Kapur
    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.

  • 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, Terrence L Sills, Paul J Fletcher, Shitij Kapur
    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.

Koichi Nakajima - One of the best experts on this subject based on the ideXlab platform.

  • randomized crossover trial of Amoxapine versus vitamin b12 for retrograde ejaculation
    International Braz J Urol, 2017
    Co-Authors: Koichi Nagao, Toshihiro Tai, Hideyuki Kobayashi, Koichi Nakajima
    Abstract:

    OBJECTIVE To compare the efficacy and safety of Amoxapine and vitamin B12 for treating retrograde ejaculation (RE). MATERIALS AND METHODS Between May 2009 and November 2012, this open-label, randomized, crossover study enrolled 26 men suffering with RE at Department of Reproductive Medicine, Omori Hospital. Patients were randomly allocated into two groups (n=13 each). The Amoxapine-B12 group received Amoxapine (50 mg daily for 4 weeks, orally) followed (after a 1-week washout period) by vitamin B12 (500 μg three-times daily for 4 weeks). The B12-Amoxapine group received the opposite regimen. All pa-tients masturbated to ejaculation at least twice during each treatment period. The primary outcome was antegrade ejaculation of semen, as reported by the patient, on more than one occasion during either treatment period (defined as treatment success). Any adverse events were noted. Success rates were compared between treatments using Fisher's exact test. RESULTS One patient (B12-Amoxapine group) withdrew for personal reasons (breakdown of marital relations); all other patients completed the study. Overall success rate was 88% (22/25). Success rate was higher for Amoxapine than for vitamin B12 (80%, 20/25 vs 16%, 4/25; P<0.0001). 18 patients were responsive to Amoxapine but not to vitamin B12, 2 patients were responsive to vitamin B12 but not Amoxapine, 2 patients were responsive to both drugs, and 3 patients had no response to either drug. One patient (4%) reported sleepiness and 2 (8%) reported constipation while receiving Amoxapine. No adverse events were reported during vitamin B12 treatment. CONCLUSIONS Amoxapine may be an effective, safe and well-tolerated therapy for RE.

  • Randomized Crossover Trial of Amoxapine Versus Vitamin B12 for Retrograde Ejaculation.
    International braz j urol : official journal of the Brazilian Society of Urology, 2017
    Co-Authors: Koichi Nagao, Toshihiro Tai, Hideyuki Kobayashi, Koichi Nakajima
    Abstract:

    OBJECTIVE To compare the efficacy and safety of Amoxapine and vitamin B12 for treating retrograde ejaculation (RE). MATERIALS AND METHODS Between May 2009 and November 2012, this open-label, randomized, crossover study enrolled 26 men suffering with RE at Department of Reproductive Medicine, Omori Hospital. Patients were randomly allocated into two groups (n=13 each). The Amoxapine-B12 group received Amoxapine (50 mg daily for 4 weeks, orally) followed (after a 1-week washout period) by vitamin B12 (500 μg three-times daily for 4 weeks). The B12-Amoxapine group received the opposite regimen. All pa-tients masturbated to ejaculation at least twice during each treatment period. The primary outcome was antegrade ejaculation of semen, as reported by the patient, on more than one occasion during either treatment period (defined as treatment success). Any adverse events were noted. Success rates were compared between treatments using Fisher's exact test. RESULTS One patient (B12-Amoxapine group) withdrew for personal reasons (breakdown of marital relations); all other patients completed the study. Overall success rate was 88% (22/25). Success rate was higher for Amoxapine than for vitamin B12 (80%, 20/25 vs 16%, 4/25; P