Autism is a lifelong neurodevelopmental disorder significantly on the rise worldwide. Prevalence rate increased dramatically from 1 case/10000 in the early 90’s to 1 case/110 in 2011. The diagnosis is characterized by three main domains: dysfunction in social interaction, communication impairment and repetitive behaviors. Selective Serotonin Reuptake Inhibitors (SSRIs) are currently the drug class of choice for treating autism symptoms. The major drawback of SSRIs is that they take several weeks to become therapeutically efficient. Co-administration of SSRIs with 5-HT1B/1D receptor antagonists proved to be advantageous over SSRIs alone with respect to the magnitude of brain serotonin levels produced. The theory is that the acute blockade of 5-HT1B/1D receptor would prevent the negative feedback these autoreceptors exert normally on serotonin release and hence enhance the efficiency of SSRIs (i.e. synergistic effect). We hypothesize to incorporate the dual pharmacophoric profile of serotonin reuptake inhibition and 5-HT1B/1D antagonism in one single molecule carrying dual functionalities. A library of 12 virtual hybrids was successfully designed. The organic synthesis of two chosen hybrids was completed with full structure elucidation, including elemental analysis and proton-Nuclear Magnetic Resonance.
The main outcome of the study is obtaining an unprecedented library of novel hybrid molecules combining serotonin reuptake inhibition with 5HT1B/1D antagonism in one single molecule. In addition, establishing chemical synthesis and other foundation materials needed for further investigation (In vitro and in vivo pharmacological evaluation) towards our ultimate goal of developing new therapeutic line of autism, where no other lines of treatment have been consistently successful.
"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."
"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."
"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."
"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."
"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."
"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."
"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."
"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."
"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."
"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."
"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."
"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."
"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."
"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."
"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."
"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."
"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."
"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."
"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."
"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."