ABSTRACT
A simple, precise, accurate stability-indicating gradient reversed-phase high-performance liquid chromatographic (RP-HPLC) method was developed for the quantitative determination of zotepine (ZTP) in bulk and pharmaceutical dosage forms in the presence of its degradation products (DPs). The method was developed using Phenomenex C18 column (250 mm ~ 4.6 mm i.d., 5 mm) with a mobile phase containing a gradient mixture of solvents, A (0.05%trifluoroacetic acid (TFA), pH ? 3.0) and B (acetonitrile). The eluted compounds were monitored at 254 nm;the run time was within 20.0 min, in which ZTP and its DPs were well separated, with a resolution of 41.5. The stress testing of ZTP was carried out under acidic, alkaline, neutral hydrolysis, oxidative, photolytic and thermal stress conditions. ZTP was found to degrade significantly in acidic, photolytic, thermal and oxidative stress conditions and remain stable in basic and neutral conditions. The developed method was validated with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness as per ICH guidelines. This method was also suitable for the assay determination of ZTP in pharmaceutical dosage forms. The DPs were characterized by LC-MS/MS and their fragmentation pathways were proposed.
ABSTRACT
Background: Schizophrenia is a functional psychosis with severe personality changes and thought disorders without cerebral damage. No reports are available in literature regarding efficacy and tolerability of atypical antipsychotic drug zotepine over olanzapine a preferred drug worldwide for the treatment of schizophrenia. Therefore, present study is undertaken to evaluate efficacy, tolerability and cost effectiveness of zotepine over olanzapine in patients suffering from schizophrenia. Methods: A prospective, randomized, single blind, parallel, 6 weeks clinical study was conducted on a total of 112 patients, of schizophrenia attending psychiatry outpatient department at G. R. Medical College, Gwalior, India randomized into two groups (56 in each). Patients received either olanzapine (10-20mg) or zotepine (75-150mg) per day for a period of 6 week. Efficacy was measured by Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI) scale whereas tolerability was measured by dropout rate and frequency of adverse effects. Cost effectiveness was calculated in terms of cost incurred for improvement at the end of treatment period. Results: Both the drugs showed significant (P<0.05) improvement in PANSS total score as compared to their respective baseline scores however, there was no significant difference between the two groups (P>.0.05). Olanzapine showed significantly better (P<0.05) positive subscale and CGI scale score improvement as well as response rate when compared to zotepine. Incidences of adverse effects like weight gain, somnolence and hyperglycemia were 42, 32 and12 % respectively with olanzapine and 39, 30 and 9% respectively with zotepine with no significant difference (P>0.05) between the two groups. Incidence of akathisia and drop out (16% and 23%) with zotepine were significant (P<0.05) as compared to olanzapine (2% and 11%) respectively. Conclusions: Though the efficacy of both the drugs is comparable, olanzapine appears to have better tolerability and cost effectiveness than zotepine in patients of schizophrenia.
ABSTRACT
Objective To observe the impact of zotepine on the excitatory synaptic response and long term potentiation (LTP) of dentate gyrus neurons.Methods Male rabbits ( n = 20) weighting about 2.5 ～ 3.5 kg were divided into four groups randomly ( n = 5 ): control, zotepine 1.0, zotepine 2.0 and zotepine 5.0.To each rabbit,there were 60 results during 120 min.Population spike(PS) amplitude and excitory postsynaptic potential (EPSP) slope were used to be the indexes of the excitatory synaptic response of dentate gyrus neurons.The sequence was base response ( at the beginning), intraperitoneal injection of 0.5ml dimethylsulfoxide or 0.5ml zotepine-dimethylsulfoxide solution ( 1.0,2.0,5.0 mg/kg of zotepine dosage) ( after 30 min) and titanic stimulation (after 90 min).Results To 4 groups,the PS amplitude and EPSP slope after single stimuli were not significantly different from those before single stimuli.In control group, the PS amplitude and EPSP slope after titanic stimulation[(0.68 ± 0.052)mV and(0.633 ± 0.024 )mV/ms] were significantly different from those before injection[(0.266 ±0.008) mV and(0.246 ±0.010) mV/ms] (P＜0.05 ～0.01 ) ,and LTP were induced.LTP were not induced after titanic stimulation in group zotepine 1.0,2.0 and 5.0.After titanic stimulation, the PS amplitude and EPSP slope in group zotepine 5.0[(0.277 ±0.008)mV and(0.296 ±0.007) mV/ms] were significantly different from those in group control(P＜ 0.05).Conclusion Zotepine had little effect on the excitatory synaptic response of dentate gyrus neurons after single stimuli in perforant path, while it blocked the induction of LTP in perforant path-dentate gyrus pathway.
ABSTRACT
Atypical antipsychotic drugs have less extra pyramidal side effects and are more effective to control the clinical manifestations of schizophrenia. However, their use may be associated to a higher incidence of weight gain, dyslipidemia, metabolic syndrome, glucose intolerance and type 2 diabetes mellitus. We performed a systematic literature search to evaluate the risk of type 2 diabetes mellitus incidence associated to the use of atypical antipsychotic drugs, compared to conventional treatment. If users of all types of atypical antipsychotic drugs are compared with users of conventional treatment, no significant differences in the incidence of type 2 diabetes mellitus were observed. If individual drugs are evaluated, clozapine and risperidone are associated with a higher risk of diabetes than haloperidol. Quetiapine is associated with a lower risk of diabetes than conventional treatment. The quality of the evidence found was low; therefore, new studies should been performed.