Allopurinol
Effect of Wen-Pi-Tang extract on lung damage by influenza virus infection.

Yokozawa T, Sekiya M, Cho EJ, Kurokawa M, Shiraki K.

Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan. yokozawa ms.toyama-mpu.ac.jp

The effect of Wen-Pi-Tang extract on influenza virus infection in mice was investigated. The administration of Wen-Pi-Tang extract at a dose of 100mg/kg body wt. for 8 consecutive days to influenza virus-infected mice reversed the lack of body wt. gain and prevented the increase in lung weight caused by the infection in comparison with uninfected mice, while allopurinol, a xanthine oxidase (XOD) inhibitor, did not show these effects. The serum levels of uric acid and allantoin in influenza virus-infected mice were reduced by Wen-Pi-Tang extract administration. Moreover, Wen-Pi-Tang extract reduced the uric acid level more as the dose increased, although it exerted lower activity than allopurinol. The XOD activity of the lungs was elevated by influenza virus infection, but Wen-Pi-Tang extract administration inhibited this activity, indicating prevention of lung damage by oxygen free radicals generated by XOD. After the administration of Wen-Pi-Tang extract to influenza virus-infected mice, the lung superoxide dismutase activity was not significantly different from that of uninfected mice, whereas lung catalase activity was lower in the former than the latter, but slightly higher than that of influenza virus-infected mice, suggesting that Wen-Pi-Tang extract may prevent the generation of highly toxic hydroxyl radicals in the lung. In addition, the administration of both Wen-Pi-Tang extract and allopurinol reduced the degree of lung consolidation caused by influenza virus infection. In particular, Wen-Pi-Tang extract reduced the consolidation score in a dose-dependent manner and more markedly than allopurinol did. This study suggests that Wen-Pi-Tang extract could improve pathological conditions of the lungs induced by influenza virus infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15636176&dopt=Abstract allopurinol Zyloprim



Allopurinol
Trypanosoma brucei: expression of multiple purine transporters prevents the development of allopurinol resistance.

Natto MJ, Wallace LJ, Candlish D, Al-Salabi MI, Coutts SE, de Koning HP.

Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Joseph Black Building, Glasgow G12 8QQ, UK.

Allopurinol is a hypoxanthine analogue used to treat Leishmania infections that also displays activity against the related parasite Trypanosoma brucei. We have investigated the ease by which resistance to this drug is established in Trypanosoma brucei brucei and correlated this to the mechanisms by which it is accumulated by the parasite. Long-term exposure of procyclic T. b. brucei to 3mM allopurinol did not induce resistance. This appears to be related to the fact that allopurinol was taken up through two distinct nucleobase transporters, H1 and H4, both with high affinity for the drug. The apparent K(m) for [(3)H]allopurinol transport by H4 (2.1+/-0.4muM) was determined by expressing the encoding gene in Saccharomyces cerevisiae. Long-term allopurinol exposure did not change K(m) (hypoxanthine), K(i) (allopurinol), or V(max) values of either H1 or H4 transporters and the cells retained their ability to proliferate with hypoxanthine as sole purine source. This study shows that transport-related resistance to purine antimetabolites is not easily induced in Trypanosoma spp. as long as uptake is mediated by multiple transporters.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15687014&dopt=Abstract allopurinol Zyloprim



Allopurinol
Beneficial antipsychotic effects of allopurinol as add-on therapy for schizophrenia: a double blind, randomized and placebo controlled trial.

Akhondzadeh S, Safarcherati A, Amini H.

Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran.

There is a large amount of data showing that adenosine plays a role opposite to dopamine in the brain. Adenosine agonists and antagonists produce behavioral effects similar to dopamine antagonists and dopamine agonists, respectively. Allopurinol, a well-known hypouricemic drug that inhibits xantine oxidase, has been used as an add-on drug in the treatment of poorly responsive schizophrenic patients. Indeed, the neuropsychiatric effects of allopurinol in schizophrenia have been suggested to be secondary to its inhibitory effect of purine degradation, enhancing adenosinergic activity. The purpose of the present investigation was to assess the efficacy of allopurinol as an adjuvant agent in the treatment of chronic schizophrenia in an 8-week double blind and placebo controlled trial. Eligible participations in the study were 46 patients with schizophrenia. All patients were inpatients and were in the active phase of the illness, and met DSM-IV criteria for chronic schizophrenia. Patients were allocated in a random fashion, 23 to haloperidol 15 mg/day plus allopurinol 300 mg/day and 23 to haloperidol 15 mg/day plus placebo. Although both protocols significantly decreased the score of the positive, negative and general psychopathological symptoms over the trial period, the combination of haloperidol and allopurinol showed a significant superiority over haloperidol alone in the treatment of positive symptoms, general psychopathology symptoms as well as PANSS total scores. The means of Extrapyramidal Symptoms Rating Scale for the placebo group were higher than in the allopurinol group over the trial, and the differences were significant in weeks 6 and 8. A significant difference was observed between the overall mean biperiden dosages in two groups. The results of this study suggest that allopurinol may be an effective adjuvant agent in the management of patients with chronic schizophrenia. Nevertheless, results of larger controlled trials are needed, before recommendations for a broad clinical application can be made.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15694232&dopt=Abstract allopurinol Zyloprim



Allopurinol
A Clinical Trial of Adjuvant Allopurinol Therapy for Moderately Refractory Schizophrenia.

Brunstein MG, Ghisolfi ES, Ramos FL, Lara DR.

From the Department of Biochemistry, Health Basic Science Institute (Instituto de Ciencias Basicas da Saude), Federal University of Rio Grande do Sul (Universidade Federal do Rio Grande do Sul) (Drs. Brunstein and Ghisolfi); and the Departments of Biochemistry and Psychiatry, Catholic University of Rio Grande do Sul (Pontificia Universidade Catolica do Rio Grande do Sul) (Drs. Ghisolfi and Lara and Ms. Ramos), Porto Alegre, Brazil.

OBJECTIVE: To evaluate the xanthine oxidase inhibitor allopurinol as an adjuvant treatment for patients with moderately refractory schizophrenia, with the objective of increasing the endogenous pool of purines, including the neuro-modulator adenosine. METHOD: A double-blind, placebo-controlled, crossover clinical trial of add-on allopurinol (300 mg b.i.d.) for poorly responsive schizophrenia or schizoaffective disorder (DSM-IV criteria) was conducted. Thirty-five patients were enrolled, of whom 22 completed the 12 weeks of the study. Eighteen of these patients also completed a P50 evoked potential evaluation. RESULTS: Allopurinol was well tolerated and produced significant improvement in Positive and Negative Syndrome Scale (PANSS) total, positive, negative, and general scores, particularly for positive symptoms compared with baseline and with placebo phase. Nine patients improved more than 20% in PANSS total score during allopurinol treatment, whereas none responded in the placebo phase. Responders had a shorter duration of illness than nonresponders. P50 auditory sensory gating failed to improve with allopurinol treatment. CONCLUSIONS: Allopurinol was an effective and well-tolerated adjuvant treatment for poorly responsive schizophrenia, especially for refractory positive symptoms.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15705007&dopt=Abstract allopurinol Zyloprim



Allopurinol
Reduction of acute cisplatin ototoxicity and nephrotoxicity in rats by oral administration of allopurinol and ebselen.

Lynch ED, Gu R, Pierce C, Kil J.

Sound Pharmaceuticals, Inc., Research and Development, 4010 Stone Way N, Suite 120 Seattle, WA 98103, USA.

Cisplatin ototoxicity has been associated with the generation of toxic levels of reactive oxygen species (ROS) which can lead to injury or loss of outer hair cells in the organ of Corti, damage to the stria vascularis, and loss of spiral ganglion cells, resulting in permanent hearing loss. In an attempt to reduce the formation of ROS and to bolster the innate oxidative stress defenses of the cochlea, we tested individual and combined formulations of allopurinol, a xanthine oxidase inhibitor, and ebselen, a glutathione peroxidase mimic. We used an acute cisplatin toxicity rat model (16 mg/kg i.p.) to analyze allopurinol and ebselen alone and in combination for their ability to reduce cisplatin associated hearing loss and nephrotoxicity. The results from our studies indicate that a combined formulation of ebselen and allopurinol affords significant protection to the cochlea and kidney from cisplatin toxicity. In the cochlea, protection is dependent on the preservation of outer hair cell number, while in the kidney, protection is associated with the preservation of proximal tubular epithelia. Further evaluation of the chemoprotective effects of ebselen and allopurinol on cisplatin side effects in the presence of tumor appears warranted.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15721563&dopt=Abstract allopurinol Zyloprim



Allopurinol
Clinical and serological follow-up in dogs with visceral leishmaniosis treated with allopurinol and sodium stibogluconate.

Pasa S, Toz SO, Voyvoda H, Ozbel Y.

Department of Internal Medicine, Faculty of Veterinary, University of Adnan Menderes, Aydin 09016, Turkey.

Seven dogs with parasitologically proven clinical visceral leishmaniosis (Leishmania infantum infection) were treated with a combination of allopurinol and sodium stibogluconate. The dogs received first orally 15mg/kg of allopurinol every 12h until the clinical signs improved, in the following 1 month period allopurinol at same dose and subcutaneously 30mg/kg of sodium stibogluconate combination were given daily and at the end of the combined treatment, allopurinol was continued alone at the same dose till the end of 8 months. During the treatment period, dogs were supported by additional proteins, vitamins, and minerals. A long acting insecticide (collar or drop) was also used in order to prevent further parasite transmission. Follow-up was maintained by clinical, clinicopathological evaluation, and parasitological examination of lymph node, serology using the indirect immunofluorescent antibody test (IFAT). Before treatment commenced, the most important clinical signs were exfoliative dermatitis, ulcerations, peripheral lymhadenopathy, pale mucous membranes, weight loss, and ocular lesions. Clinicopathological findings included commonly anaemia, hyperproteinaemia, hyperglobulinaemia and hypoalbuminaemia. Before the treatment, amastigotes were seen in six of the seven dogs by examination of lymph node aspiration, and IFAT-titers were positive in all dogs. At the end of 8 months treatment, remission of clinical signs, restoration to normal of clinicopathological abnormalities were noticed. Lymph node aspiration was performed on three out of the seven dogs at the end of the treatment because of the very small sizes of the lymph nodes, and no amastigotes were observed. Although the mean IFAT-titer of the dogs were significantly (P<0.001) lower compared with pretreatment, IFAT-titers of dogs were still positive. No relapses occurred during treatment period and a 6-24-month duration after the end of therapy. Based on the above results, long-term use of allopurinol combined with sodium stibogluconate together with support treatment concluded to have enough therapeutic efficacies in the treatment of dogs with visceral leishmaniosis. Observations of the cases for possible relapses were still going on and insecticide application was carefully carrying on in order preventing a possible re-infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15740861&dopt=Abstract allopurinol Zyloprim