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Drug Discovery for Mental Disorders: Preclinical Studies of Peruvian Botanicals

治疗精神疾病的药物发现：秘鲁植物药的临床前研究

基本信息

批准号：
8411557
负责人：
Abraham Jaime Vaisberg
金额：
$ 10.8万
依托单位：
UNIVERSIDAD PERUANA CAYETANO HEREDIA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-05-27 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8411557
关键词：
Academia Acids Adherence Animal Model Anti-Anxiety Agents Antidepressive Agents Antipsychotic Agents Anxiety Area Behavior Behavioral Behavioral Model Biological Assay Biological Availability Biological Factors Botanicals Caring Cell model Clinical Cognition Collection Costs and Benefits Country Disease Dose Drug Industry Early Intervention Failure Family Fractionation Goals Healed Health Services Accessibility Human Income Institution Interdisciplinary Study International Knowledge Lead Lethal Dose 50 Libraries Literature Manic Medical Mental Depression Mental disorders Methods Modeling Molecular Molecular Models Molecular Target Mus National Institute of Mental Health Nature New Agents Outcome Patients Peru Pharmacologic Substance Pharmacotherapy Plant Extracts Plants Preclinical Drug Evaluation Preparation Protocols documentation Psychotropic Drugs Reporting Research Research Personnel Research Training Rodent Running Sampling Schizophrenia Source Staging Swimming Testing Therapeutic Agents Therapeutic Effect Traditional Medicine Transgenic Organisms Treatment outcome Validation Work behavior test disabling disease drug candidate drug discovery healing high throughput screening improved in vivo innovation insight interest molecular modeling multidisciplinary novel novel strategies novel therapeutics preclinical study prepulse inhibition public health relevance research study response screening sedative small molecule libraries tool

项目摘要

DESCRIPTION (provided by applicant): This proposal is part of a long {range effort} directed to the discovery of new pharmaceuticals from Peruvian flora traditionally used for the treatment of mental disorders. {Our main hypothesis is that plants ancestrally used by Peruvian traditional healers for treating mental illnesses are a source of novel therapeutics for these disorders. We specifically hypothesize that: 1) it is possible to isolate bioactive principles from these plants;2) rodent behavioral models are a good start point tool for screening/validation and for further prioritization of research on those activities; 3) the isolated lead compounds will be superior to those obtained from chemical libraries in terms of better bioavailability and less secondary effects; 4) the pharmacological information obtained will help to further understand the traditional medicine conceptualization of mental disorders in Peru. Previous studies have led us} to collect information on the traditional use of plants for the treatment of mental disorders in several Peruvian localities and geographical regions. We currently have extracts from 475 plant collections corresponding to 265 species from 87 different plant families. These plants are traditionally used for one or more of the following activities: antipsychotic, antidepressant, anxiolytic and sedative. {Importantly}, about 65% of those species have never been described in the scientific literature for their potential effects on the modulation of behavior. About {20%} of these plant extracts have been screened so far to validate its traditional medical use with behavioral tests in mice. To date we have identified {70} extracts having one or more potential psychotropic activity ({54} antipsychotic, {40} anxiolytic and {17} antidepressant). {Dose-response curves have been run for 9 of these extracts.} In this R21 we are proposing to {run 30 additional dose-response curves and pursue the activity guided fractionation of at least 1 extract. We have especial interest in developing or testing} new methods for the screening and bioassay guided fractionation of our extracts, in order to identify novel agents that could be candidate drugs or lead compounds for mental disorders. Also, we aim to get further insight on the Peruvian traditional medicine conceptualization of mental disorders, by comparing the pharmacological/behavioral results obtained in our experiments with the reported/interpreted traditional use. A multidisciplinary group of {professionals, leaders in their area of expertise,} has been invited to participate in this R21, which will end up in the preparation of an R01 proposal. Screening natural product extracts for mental disorders has led to the discovery of therapeutic agents in use today, and, although discovery of a new agent is obviously an ambitious goal, there are numerous factors that support the likelihood of being able to successfully identify novel agents that are candidate drugs or lead compounds for mental disorder treatment. These factors include the innovative screening approach, the uniqueness of our natural product library, the multidisciplinary nature of the project, and the expertise of the team of investigators and consultants.