Olanzapine enhances the effect of conventional drugs in chemotherapy inducing nausea and vomiting: A randomized clinical trial.

Background: Chemotherapy inducing nausea and vomiting (CINV) is one of the significant side effects of anti-cancer treatment, and its full prevention is a potential challenge. This study was done to specify the effect of olanzapine in this setting. Methods: In this randomized, double-blind, clinical trial study, olanzapine was compared with a placebo in combination with dexamethasone and granisetrone in patients with cancer. Patients in the intervention group received dexamethasone , granisetron and olanzapine. Patients in the control group received a placebo instead of olanzapine. Overall, acute nausea and vomiting prevention were the primary and secondary end points; complete response (no nausea,no vomiting) in the delayed period of chemotherapy was the third end point. Response to treatment was evaluated by the Functional Living Index Emesis (FLIE) questionnaire completion in the first, the third and the fifth of chemotherapy. Results: Percentage reduction in mean±SD nausea and vomiting in the overall phase (0-120 hours) of intervention group compared to the control group respectively were 29.94±2.06, 69.75±2.32 [(57.93% reduction (p<0.001)]. For the acute phase (0-24 hours) were 26.08±2.36, 51.85±2.24 [(47.21% reduction (p<0.001)], for the delayed phase (24-120 hours), were 31.26±2.57, 67.91±2.12 ,[(55.11% reduction;(p<0.001)] respectively. Conclusion: Olanzapine, along with dexamethasone and granisetron, significantly reduced vomiting and nausea in patients undergoing chemotherapy. No adverse event of olanzapine was observed in the patients.

Venlafaxine can reduce the migraine attacks as well as amitriptyline: A noninferiority randomized trial.

OBJECTIVES: Migraine, as a primary headache, is among the leading causes of disability worldwide. The present study aimed at comparing the effects of venlafaxine (VLF) and amitriptyline (AMT) reducing the severity and the number of migraine attacks. METHODS: Patients with complaints of migraine attacks were randomly divided into two groups. The first group received amitriptyline at a dose of 25 mg every night, and the second group received venlafaxine at a dose of 37.5 mg daily. The duration of treatment was eight weeks. RESULTS: Eighty patients participated in the current study, out of which 57.5% were females. The mean age of the participants was 33 years, and the mean duration of disease was eight years. Both amitriptyline and venlafaxine significantly reduced the number of attacks per month (AMT: from 10.98 to 2.98, VLF: from 9.98 to 3.18), and six-item Headache Impact Test (HIT-6) score (AMT: from 67.78 to 49.73, VLF: from 66.65 to 48.88), and no significant difference was observed between the two drugs. The results demonstrated no significant relationship between age or disease duration with the score of the HIT-6. The decrease rate in the score of the HIT-6 in males was higher than that of females which shows the modifier role of the gender. Besides, it is noteworthy to mention that the adverse effects of amitriptyline exceeded the venlafaxine among the patients. CONCLUSION: The effectiveness of AMT and VLF in terms of their potential to reduce the intensity and duration of headaches was more noticeable in male patients than female patients. In terms of adverse drug reactions, patients in the amitriptyline group complained more about adverse drug reactions (ADR) than patients in the venlafaxine group. It seems that in similar conditions, venlafaxine could have priority over amitriptyline in migraine prophylaxis.

A combined Fisher and Laplacian score for feature selection in QSAR based drug design using compounds with known and unknown activities.

Quantitative structure-activity relationship (QSAR) is an effective computational technique for drug design that relates the chemical structures of compounds to their biological activities. Feature selection is an important step in QSAR based drug design to select the most relevant descriptors. One of the most popular feature selection methods for classification problems is Fisher score which aim is to minimize the within-class distance and maximize the between-class distance. In this study, the properties of Fisher criterion were extended for QSAR models to define the new distance metrics based on the continuous activity values of compounds with known activities. Then, a semi-supervised feature selection method was proposed based on the combination of Fisher and Laplacian criteria which exploits both compounds with known and unknown activities to select the relevant descriptors. To demonstrate the efficiency of the proposed semi-supervised feature selection method in selecting the relevant descriptors, we applied the method and other feature selection methods on three QSAR data sets such as serine/threonine-protein kinase PLK3 inhibitors, ROCK inhibitors and phenol compounds. The results demonstrated that the QSAR models built on the selected descriptors by the proposed semi-supervised method have better performance than other models. This indicates the efficiency of the proposed method in selecting the relevant descriptors using the compounds with known and unknown activities. The results of this study showed that the compounds with known and unknown activities can be helpful to improve the performance of the combined Fisher and Laplacian based feature selection methods.

Effect of Buspirone, Fluoxetine and 8-OH-DPAT on Striatal Expression of Bax, Caspase-3 and Bcl-2 Proteins in 6-Hydroxydopamine-Induced Hemi-Parkinsonian Rats.

PURPOSE: The exact pathogenesis of sporadic parkinson's disease (PD) is still unclear. Numerous evidences suggest involvement of apoptosis in the death of dopaminergic neurons. In this study we investigated the effect of sub-chronic administration of buspirone, fluoxetine and 8-hydroxy-2-[di-n-propylamino]tetralin (8-OH-DPAT) in 6-hydroxydopamine (6-OHDA)-lesioned rats and assayed striatal concentrations of apoptotic (Bax, Caspase3) and anti-apoptotic (Bcl-2) proteins. METHODS: 6-OHDA (8µg/2µl/rat) was injected unilaterally into the central region of the substantia nigra pars copmacta (SNc) of male Wistar rats and then, after 21 days lesioned rats were treated with intraperitonel (i.p) 1 mg/kg injections of buspirone, fluoxetine and 8-OH-DPAT for 10 consecutive days. Striatum of rats was removed at tenth day of drugs administration and were analyzed by western blotting method to measure Bax, caspase3 and Bcl-2 expression. RESULTS: The results showed that the expression of Bax and caspase3 proteins was increased three weeks after 6-OHDA injection while they were decreased significantly in parkinsonian rats which were treated by buspirone, fluoxetine and 8-OH-DPAT. Bcl-2 was decreased and increased in parkinsonian rats and parkinsonian rats treated with buspirone, fluoxetine and 8-OH-DPAT, respectively. CONCLUSION: Our study indicates that sub-chronic administration of serotonergic drugs such as buspirone, fluoxetine and 8-OH-DPAT restores striatal concentration of apoptotic and anti-apoptotic factors to the basal levels of normal non-lesioned rats. We suggest that these drugs can be used as a potential adjunctive therapy in PD through attenuating neuronal apoptotic process.

Effect of acute and chronic administration of carbamazepine on Cisplatin-induced hyperalgesia in rats.

BACKGROUND: Cisplatin is an effective antineoplastic drug used extensively in the treatment of malignancies. It induces painful peripheral neuropathy at high doses. OBJECTIVES: The aim of this study was to investigate the effect of carbamazepine (CBZ) on cisplatin-induced peripheral neuropathic pain by using the tail-flick test. MATERIALS AND METHODS: The study was performed using male Wistar rats weighing 180-200 g. Neuropathic pain was induced by intraperitoneal (IP) administration of cisplatin (5 mg/kg). The effect of oral (PO) CBZ administration (5, 10, and 15 mg/kg) on cisplatin-induced pain was assessed using the tail-flick test. RESULTS: Our results showed that cisplatin (5 mg/kg, IP) induced egregious pain (P < 0.01) on day 15. Acute administration of CBZ (5, 10, and 15 mg/kg, PO) caused significant (P < 0.05) increase in tail-flick time latency in a dose-dependent manner, in comparison with that observed in the control group. Furthermore, chronic administration of CBZ (5, 10, and 15 mg/kg, PO) increased (P < 0.05) the pain threshold on days 5 and 10. The analgesic effect of morphine (5 mg/kg, IP) was greater than that after acute CBZ administration (5, 10, and 15 mg/kg, PO). CONCLUSIONS: Our results showed that both acute and chronic CBZ administration attenuated cisplatin-induced pain. We suggest that CBZ can be used clinically for alleviating cisplatin-induced neuropathic pain in cancer patients, without any limitations such as tolerance to analgesic effect.