AN OVERVIEW ON PRECLINICAL EVALUATION TECHNIQUES OF NOOTROPIC AGENTS
Renu Singh*, Saumya Das, Sanjita Das
Institute of Pharmaceutical Technology, NIET,
Greater Noida, U.P., 201306.
Cognitive deficits have long been recognized as severe and consistent neurological disorders associated with numerous psychiatric and neurodegenerative states such as Alzheimer’s disease. Dementia is one of the age-related mental problems, and a characteristic symptom of Alzheimer’s disease. Alzheimer’s disease (AD) is a progressive neurodegerative disorder which affects older individuals and may progress to a totally vegetative state. Atrophy of cortical and sub-cortical areas is associated with deposition of β-amyloid protein in the form of senile plaques and formation of neurofibrillary tangles. There is marked cholinergic deficiency in the brain, though other neurotransmitter systems are also affected. Various measures to augement cholinergic transmitter in the brain have been tried. The relatively cerebroselective anti-ChEs have been approved for clinical use. Nootropic agents are clinically used in situations where there is organic disorder in learning abilities and for improving memory, mood and behavior, but the resulting side-effects associated with these agents have made their utility limited. Many experimental models are currently available for the evaluation of agents that affect learning and memory processes. In-vitro methods inhibition of acetylcholinesterase activity is measured by determining IC50 with the help of Log probit analysis. In ex-vivo cholinesterase inhibition method the dose response relationship determined for drugs such as physostigmine and tacrine Agents which are H3 receptor agonist are evaluated for [3H] Ach release activity in rat using rat brain slices. The binding affinity of potential nicotinic cholinergic agonist in brain using agonist ligand is determined by [3H]-N- methyl carbamylcholine binding nicotinic cholinergic receptors in rat frontal cortex. In In-vivo methods the inhibitory passive avoidance the test are carried on animals to test the learning and memory capacity of animal by suppressing a particular behavior. It includes step down, step through, two compartment test, up-hill avoidance, scopolamine induced test, and ischemia induced amnesia, memory impairments in basal forebrain. In active avoidance conditioned stimulus is given to the animal, which gives noxious stimulus as a result. It includes runway avoidance, shuttle box avoidance, jumping avoidance. In discrimination learning animals have no choice between the conditioned stimuli. Studies on aged monkeys provides additional advantage for neurobehavioral animal model of aging in that many of behavioral processes thought to be affected by aging.
Reference Id: PHARMATUTOR-ART-1308
Research during the past two decades has unfolded the behavioral, neurobiological and cellular basis of learning and memory processes. Learning is defined as the acquisition of information and skills, and subsequent retention of that information is called memory. Accordingly, effects of a wide variety pharmacological agents or brain lesions on the cognitive behavior have been studied and most validly interpreted as ‘enhancement or impairment’of learning and memory processes. Consequently, “nootropics” are agents that enhance the cognitive skills and “amnestics” are agents that disrupt the learning and memory processes. Nootropics are also referred as smart drugs, memory enhancers, and cognitive enhancers. They are reported to improve mental function such as cognition, memory, intelligence, motivation, attention and concentration They are thought to be work by altering the availability of brains supply of. neurochemicals, by improving the brains oxygen supply or by stimulating nerve growth1. The concept and definition of a Nootropic drug was first proposed by Romanian Dr. Corneliu e. Giurgea. He derived the term nootropics from the Greek words noos (mind) and tropein (to turn towards). The main features of nootropics drug are, the enhancement, at least under same conditions of learning acquisition as well as resistance of learned behaviors to agents that tend to impair them, the facilitation of inter hemispheric flow of information, partial enhancement of the general resistance of the brain and particularly its resistance to physical and chemical injuries and increase in the efficacy of the tonic cortico sub cortical control mechanisms. During the past 30 years, the PIR nootropics have been used to treat an amazingly broad range of human ailments and condition either alone or with other drugs, with moderate to major benefit. Nootropics have been used to treat various forms of the dementia and organic brain syndrome.
They are used successfully to treat dyslexia, epilepsy and age associated memory impairment. PIR- nootropics have successfully treated vertigo, alcohol withdrawal, cerebrovascular insufficiency and hypoxia. They have shown benefit in normalizing blood flow parameters, decreased platelet aggregation, increased RBC deformability, decreased adherence of damaged and sickle cell RBCs to endothelium and increased prostacyclin production and activity. The racetams (nootropics) are cerebral homeostatic normalizers, neuroprotectants, cerebral metabolic enhancers and brain integrative agents. They enhance brain energy, especially under deficit condition eg. hypoxia, chemical toxicity or impaired cerebral microcirculation. They preserve, protect and enhance synaptic membrane and receptor structure and plasticity. They enhance brain integration horizontally by increased coupling of the cerebral hemisphere and vertically by enhancing cerebral connection with and tonic control of the limbic system through nootropics effect on the hippocampus a major link between cerebrum and limbic system. Over 30 years have passed since the Nootropics revolution quietly began with the development of the Piracetam (PIR) in the late 1960’s. The second wave of this pharmacologic revolution occurred in the late 1970’s with the development of Oxiracetam (OXR), Pramiracetam (PRM), and Aniracetam (ANR). The action of the PIR nootropics has been studied in a broad range of animals; goldfish, mice, rats, guinea pigs, rabbits, dogs, cats,, monkeys and humans. The toxicity of PIR and its cousins is amazingly low, almost non-existant. PIR nootropics are among the toxicologically safest drug ever developed. In 2006 there were 26.6 million suffers worldwide of Alzheimer’s disease (AD) 1-2.
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