A case of improvement of clozapine-induced low leukocyte counts by adenine, cepharanthin and ninjin-yoei-to in a patient with treatment-resistant schizophrenia.

BACKGROUND: Although clozapine is the optimal drug for patients with treatment-resistant schizophrenia, the drug has harmful adverse effects such as leukopenia. Adenine and cepharanthine are known to be effective for radiation- or drug-induced leukopenia. Furthermore, ninjin-yoei-to, a Chinese herbal medicine, augments the production of granulocyte-macrophage colony-stimulating factor. Thus, these drugs may be useful for clozapine-induced leukopenia. CASE PRESENTATION: A 21 years-old woman with schizophrenia was hospitalized for initiation of clozapine treatment. Despite concomitant use of adenine, cepharanthine, and lithium carbonate having activities of increasing leukocytes, a decrease in leukocyte counts occurred after the initiation of clozapine. Additional administration of ninjin-yoei-to increased leukocyte counts, which prevented the development of leukopenia. CONCLUSIONS: This is the first case that concomitant use of adenine, cepharanthin, and ninjin-yoei-to exhibited the effectiveness of reversing the decrease in leukocytes caused by clozapine. Monitoring leukocyte counts and preventing leukopenia are essential for successful treatment with clozapine for refractory schizophrenia. These medicines may be a potential option for preventing clozapine-induced leukopenia.

Kamishoyosan potentiates pentobarbital-induced sleep in socially isolated, ovariectomized mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Sleep disorders are among the most common symptoms in both peri- and post-menopausal women. Kamishoyosan (KSS) is a Kampo medicine prescribed for the treatment of sleep disorders in menopausal women in Japan. However, its precise mechanism of action remains unclear. AIM OF THE STUDY: In the present study, we developed a new animal model of menopausal sleep disorders by inducing social isolation stress in ovariectomized mice. Using pentobarbital-induced sleeping time as an index, we aimed to investigate the effects of KSS and involvement of the benzodiazepine receptors. MATERIALS AND METHODS: Eight-week-old, female ddY mice were ovariectomized or subjected to a sham operation (control) and housed in social isolation or groups for 9 weeks. The animals were divided into four groups, group-housed sham-operated, isolated sham-operated, group-housed ovariectomized, and socially isolated ovariectomized. Pentobarbital (50 mg/kg) was administered intraperitoneally (i.p.). Sleeping time was considered the period between the loss of righting reflex and its return (up to 180 min). KSS was administered orally (p.o.) 60 min before the test. Diazepam and flumazenil were administered i.p. 30 and 45 min before the test, respectively. On the day after administration, the mice were euthanized, and their uteri were weighed. RESULTS: Socially isolated, ovariectomized mice had shorter sleeping times than mice in all other groups. In mice with intact ovaries, diazepam (1 mg/kg, i.p.) considerably prolonged the pentobarbital-induced sleeping time, but KSS (30-1000 mg/kg, p.o.) did not. However, KSS (100 mg/kg, p.o.) significantly prolonged the pentobarbital-induced sleeping time in socially isolated ovariectomized mice. The prolongation of sleeping time mediated by KSS was reversed by flumazenil (3 mg/kg, i.p.). CONCLUSIONS: KSS potentiated pentobarbital-induced sleep in socially isolated, ovariectomized mice, and the benzodiazepine receptors are possibly involved in its pharmacological mechanism. These findings suggest that KSS is beneficial for the treatment of menopausal sleep disorders.

Kamishoyosan reduces conditioned fear-induced freezing behavior in socially isolated ovariectomized rats.

In the present study, we investigated the effect of kamishoyosan (KSS) on conditioned fear-induced freezing in ovariectomized (OVX) rats. Socially isolated OVX rats showed the longest freezing time among the following four groups: group-housed sham-operated (Sham), isolated Sham, group-housed OVX, and isolated OVX rats. Repeated oral administration of KSS (30-300 mg/kg) reduced conditioned fear-induced freezing in socially isolated OVX rats. The reduction of freezing by KSS was reversed by flumazenil (3 mg/kg) and bicuculline (3 mg/kg). These findings suggest that the GABAA-benzodiazepine receptor complex is involved in the anxiolytic effect of KSS in socially isolated OVX rats.