Piracetam defines a new binding site for allosteric modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors.

                Glutamate receptors are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system and are important potential drug targets for cognitive enhancement and the treatment of schizophrenia. Allosteric modulators of AMPA receptors promote dimerization by binding to a dimer interface and reducing desensitization and deactivation. The pyrrolidine allosteric modulators, piracetam and aniracetam, were among the first of this class of drugs to be discovered. We have determined the structure of the ligand binding domain of the AMPA receptor subtypes GluA2 and GluA3 with piracetam and a corresponding structure of GluA3 with aniracetam. Both drugs bind to GluA2 and GluA3 in a very similar manner, suggesting little subunit specificity. However, the binding sites for piracetam and aniracetam differ considerably. Aniracetam binds to a symmetrical site at the center of the dimer interface. Piracetam binds to multiple sites along the dimer interface with low occupation, one of which is a unique binding site for potential allosteric modulators. This new site may be of importance in the design of new allosteric regulators.

Cognitive Enhancement- How much justified?

                Enhancement of human abilities is always center of attraction for all since long time. It is not uncommon that in past people used various herbs and searched for special plants which increase their strength, intellectual capabilities and life span. The main difference between past and present is at present this all search are done in specialized laboratories instead of jungles.
               Another widely debated and controversial area is athletic enhancement where athletes take various substances to enhance their athletic performance. But this gives unfair advantage to user of these substance, so no wonder we have long list of doping substances which are prohibited during athletic games.
               21st century life and tough competition in all fields have given rise to another human enhancement area, The Cognitive Enhancement. Cognitive enhancement can increase your work productivity, creativity, memory, smartness. All these factors are valuable in any business or academic field. If you take something that increases your test scores, then It can change your whole life.
               Cognitive Enhancement is same as athletic Enhancement where the person who is taking cognitive enhancers get unfair advantages. He may pop a pill and study for whole day, on other hand person who is not taking them may have to work hard to stay motivated. Unfortunately, there are no doping tests available in this field on human enhancement.
               On other hand, cognitive enhancement can be life saving for person having various neurological disease like alzheimer's disease, ADHD, Dementia, Schizophrenia, TBI. These person already struggle to function at normal levels and if taking cognitive enhancers make them able to perform at normal levels it can be miracle for them. We can't tell that this kind of people are getting unfair advantages.
              Use of cognitive enhancement by scientists is also justified because their main aim is to provide society new technologies and cures for medical conditions. Chances of Cognitively Enhanced scientist to discover something new are higher than normal scientist.
              Field of cognitive enhancement is still a matter of debate and it is not clear who should use these substances and who should not.

Nicotinic receptor subtypes and cognitive function

                         Nicotinic receptor systems are involved in a wide variety of behavioral functions including cognitive function. Nicotinic medications may provide beneficial treatment for cognitive dysfunction such as Alzheimer's disease, schizophrenia, and attention deficit hyperactivity disorder (ADHD). Nicotine has been shown to improve attentional performance in all of these disorders. Better efficacy with fewer side effects might be achieved with novel nicotinic ligands selective for particular nicotinic subtypes. To develop these novel selective nicotinic ligands it is important to use animal models to determine the critical neurobehavioral bases for nicotinic involvement in cognitive function. Nicotine-induced cognitive improvement in rats is most consistently seen in working memory tasks. We have found that both acute and chronic nicotine administration significantly improves working memory performance of rats in the radial-arm maze. The pharmacologic and anatomic mechanisms for this effect have been examined in our laboratory in a series of local drug infusion studies. Both alpha 4 beta 2 and alpha 7 nicotinic receptors in the ventral hippocampus and basolateral amygdala are involved in working memory function. Working memory impairments were caused by local infusion of either alpha 4 beta 2 or alpha 7 antagonists. Ventral hippocampal alpha 4 beta 2 blockade-induced working memory deficits are reversed by chronic systemic nicotine treatment, while ventral hippocampal alpha 7 blockade-induced working memory deficits were not found to be reversed by the same nicotine regimen. Interestingly, alpha 4 beta 2 and alpha 7 induced deficits were not found to be additive in either the ventral hippocampus or the basolateral amygdala. In fact, in the amygdala, alpha 7 antagonist cotreatment actually reversed the working memory impairment caused by alpha 4 beta 2 antagonist administration. These studies of the neural nicotinic mechanisms underlying cognitive function are key for opening avenues for development of safe and effective nicotinic treatments for cognitive dysfunction.