18 research outputs found
In vivo pharmacological evaluations of novel olanzapine analogues in rats: a potential new avenue for the treatment of schizophrenia
Olanzapine (Olz) is one of the most effective antipsychotic drugs commonly used for treating schizophrenia. Unfortunately, Olz administration is associated with severe weight gain and metabolic disturbances. Both patients and clinicians are highly interested in the development of new antipsychotics which are as effective as atypical antipsychotics but which have a lower propensity to induce metabolic side effects. In the present study, we examined two new derivatives of Olz; OlzEt (2-ethyl-4-(4′-methylpiperazin-1′-yl)-10Hbenzo[b]thieno[2,3-e][1,4]diazepine), and OlzHomo (2-ethyl-4-(4′-methyl-1′,4′-diazepan-1′-yl)-10H-benzo[b]thieno[2,3-e] [1,4]diazepine), for their tendency to induce weight gain in rats. Weight gain and metabolic changes were measured in female Sprague Dawley rats. Animals were treated orally with Olz, OlzEt, OlzHomo (3 or 6 mg/kg/day), or vehicle (n = 8), three times daily at eight-hour intervals for 5 weeks. Furthermore, a phencyclidine (PCP)-treated rat model was used to examine the prevention of PCP-induced hyperlocomotor activity relevant for schizophrenia therapy. Male Sprague Dawley rats were pre-treated with a single dose (3 mg/kg/day) of Olz, OlzEt, OlzHomo, or vehicle (n = 12), for 2 weeks. Locomotor activity was recorded following a subcutaneous injection with either saline or PCP (10 mg/kg). Olz was found to induce weight gain, hyperphagia, visceral fat accumulation, and metabolic changes associated with reduced histamatergic H1 receptor density in the hypothalamus of treated rats. In contrast, OlzEt and OlzHomo presented promising antipsychotic effects, which did not induce weight gain or fat deposition in the treated animals. Behavioural analysis showed OlzEt to attenuate PCP-induced hyperactivity to a level similar to that of Olz; however, OlzHomo showed a lower propensity to inhibit these stereotyped behaviours. Our data suggest that the therapeutic effectiveness of OlzHomo may be delivered at a higher dose than that of Olz and OlzEt. Overall, OlzEt and OlzHomo may offer a better pharmacological profile than Olz for treating patients with schizophrenia. Clinical trials are needed to test this hypothesis
State anxiety, psychological distress and positive well-being responses to yoga and aerobic exercise in people with schizophrenia
PURPOSE: Worsening of schizophrenia symptoms is related to stress and anxiety. People with schizophrenia often experience difficulties in coping with stress and possess a limited repertoire of coping strategies. A randomised comparative trial was undertaken in patients with schizophrenia to evaluate changes in state anxiety, psychological stress and subjective well-being after single sessions of yoga and aerobic exercise compared with a control condition. METHOD: Forty participants performed a single 30-min yoga session, 20-min of aerobic exercise on a bicycle ergometre at self-selected intensity and a 20-min no exercise control condition in random order. RESULTS: After single sessions of yoga and aerobic exercise individuals with schizophrenia or schizoaffective disorder showed significantly decreased state anxiety (p < 0.0001), decreased psychological stress (p < 0.0001) and increased subjective well-being (p < 0.0001) compared to a no exercise control condition. Effect sizes ranged from 0.82 for psychological stress after aerobic exercise to 1.01 for state anxiety after yoga. The magnitude of the changes did not differ significantly between yoga and aerobic exercise. CONCLUSION: People with schizophrenia and physiotherapists can choose either yoga or aerobic exercise in reducing acute stress and anxiety taking into account the personal preference of each individual.status: publishe