{"id":276,"date":"2019-10-09T22:02:57","date_gmt":"2019-10-09T16:32:57","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=276"},"modified":"2019-10-09T22:02:57","modified_gmt":"2019-10-09T16:32:57","slug":"nootropics-cerebro-active-drugs-cognition-enhancers","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/nootropics-cerebro-active-drugs-cognition-enhancers\/","title":{"rendered":"Nootropics\/ Cerebro-active drugs\/ Cognition enhancers"},"content":{"rendered":"\n<p><strong>Definition of Nootropic agents<\/strong><\/p>\n\n\n\n<p>A drug that selectively improves the efficiency\nof higher telencephalic integrative activities by:<\/p>\n\n\n\n<ul><li>Enhancement of learning and memory.<\/li><li>Facilitation of synaptic transmission.<\/li><li>Facilitates inter-hemisphere information transfer.<\/li><li>Prevents the development of memory deficits.<\/li><li>Increased tonic cortical control on subcortical areas.<\/li><\/ul>\n\n\n\n<p>Cognition is\ndefined as the processes an organism uses to organize information<\/p>\n\n\n\n<p>Concept of cognition\nrelated to reasoning, intelligence, learning.<\/p>\n\n\n\n<p>Cognitive disorders category of mental\nhealth disorders that mainly affect learning, memory, perception, and problem\nsolving<\/p>\n\n\n\n<p>It includes,<\/p>\n\n\n\n<ol><li>Amnesia<\/li><li>Dementia<\/li><li>Delirium<\/li><\/ol>\n\n\n\n<p><strong>Dementia:<\/strong> A syndrome due to disease of the\nbrain, characterized by progressive, global deterioration in intellect\nincluding Memory, Learning, Orientation, Language, Comprehension, Judgement<\/p>\n\n\n\n<p><strong>The role of Neurotransmitters in memory<\/strong><\/p>\n\n\n\n<ul><li>The\n<strong>role of acetylcholine<\/strong> in cognition\nand memory formation is well established. In the early stages of AD levels of\nAcetylcholine are reduced.<\/li><li>Accumulation\nof beta-amyloid peptide appears to be central to the degenerative changes seen\nin the brain in Alzheimer\u2019s disease. It results in the destruction of\ncholinergic neurons and a fall in acetylcholine concentration.<\/li><li>Acetylcholinesterase\nbreaks down acetylcholine in the synaptic cleft<\/li><li>Acetylcholinesterase\ninhibitors e.g. Donepezil prevent this action, thereby increasing levels of\nacetylcholine.<\/li><\/ul>\n\n\n\n<ul><li><strong>Glutamate<\/strong> -Excitatory neurotransmitter,\nallows Ca<sup>+<\/sup> to enter the cell, exciting the neuron. Excitatory\nactivity, if excessive, leads to neuronal cell death<\/li><li>&nbsp;Memantine \u00e0 a glutamate receptor antagonist which\naddresses the excitotoxic effects of glutamate by occupying NMDA receptor\nsites.<\/li><li>Memantine\ndisplaces Mg<sup>++<\/sup> from N-Methyl-D-Aspartate (NMDA) receptors, thus\nmoderating the excitatory effect of glutamate<\/li><\/ul>\n\n\n\n<p><strong>Indications\nof cognition enhancers<\/strong><\/p>\n\n\n\n<p>A various neurodegenerative disorder\nassociated with cognitive dysfunction &#8211;<\/p>\n\n\n\n<ol><li>Alzheimer&#8217;s disease<\/li><li>Senile dementia<\/li><li>Multi-infract dementia<\/li><li>Parkinson\u2019s disease<\/li><li>Stress-induced dementia<\/li><li>Attention deficit disorder<\/li><li>TIA, CVA, Stroke<\/li><li>Sequalae of head injury<\/li><\/ol>\n\n\n\n<p><strong>Classification of\nCognitive enhancers<\/strong><\/p>\n\n\n\n<p><strong>Drugs<\/strong><\/p>\n\n\n\n<ul><li>Cholinergic activators: Donepezil, Rivastigmine<\/li><li>Glutamate (NMDA) antagonist: Memantine<\/li><li>Others: Piracetam, Pyritinol(Pyrithioxine), Dihydroergotoxine (Codergocrine), Citicoline, Piribedil, etc<\/li><li>Herbs: Brahmi, Gingko biloba, etc.<\/li><\/ul>\n\n\n\n<p><strong>Cholinergic\nactivators:<\/strong><\/p>\n\n\n\n<p><strong>MOA:\n<\/strong><\/p>\n\n\n\n<ul><li><strong>Donepezil, galantamine,<\/strong> and <strong>rivastigmine<\/strong> are used in the treatment of mild to moderate\ndementia due to Alzheimer&#8217;s disease and may be helpful in the treatment of\ndementia with Lewy bodies. They enhance cholinergic function in the CNS through\nreversible inhibition of acetylcholinesterase. <\/li><li>None\nof the available drugs prevents Alzheimer\u2019s disease or modifies its pathology.<\/li><\/ul>\n\n\n\n<p><strong>Rivastigmine<\/strong><\/p>\n\n\n\n<ul><li>Carbamate derivative of\nPhysostigmine<\/li><li>Inhibits both AChE and\nBuChE-more selective to G1 isoform of AChE which is predominant in brain<\/li><li>Highly lipid-soluble \u2013CNS penetration<\/li><li>MOA: Introduces carbamyl\nresidues to AChE and renders inactive which dissociates slowly<\/li><li>Uses: Useful in mild to\nmoderate Alzheimer`s disease<\/li><li>Available as 1.5, 3, 4.5, 6 mg\ncaps orally(twice daily)<\/li><li>Transdermal patch available\napplied every 24hrs<\/li><\/ul>\n\n\n\n<p><strong>Donepezil:<\/strong><\/p>\n\n\n\n<ul><li>Cerebroselective and reversible\nanti-AChE<\/li><li>Improves Ach concentration in\ncortex especially in projecting neurons from basal ganglia to cortex<\/li><li>Improvement maintains upto2\nyears<\/li><li>A long duration of action\n(half-life \u201370 hours) and useful in severe cases of AD \u2013<strong>once daily<\/strong><\/li><\/ul>\n\n\n\n<p><strong>Galantamine:<\/strong><\/p>\n\n\n\n<p>Natural alkaloid \u2013selective inhibition of cerebral AChE\nand also direct agonistic action on Nicotinic receptors \u2013twice daily dose<\/p>\n\n\n\n<ul><li><strong>Common Adverse Effects Donepezil, Rivastigmine, Galantamine: <\/strong>nausea, vomiting, diarrhea,\nanorexia, abdominal pain, dyspepsia, headache, insomnia, vivid dreams,\ndepression, fatigue, drowsiness, dizziness, tremor, weight loss, muscle cramps,\nurinary incontinence, increased sweating, hypertension, syncope<\/li><li><strong>Infrequent or rare-<\/strong>bradycardia, heart block, seizure, agitation, hallucination, confusion,\nGI hemorrhage<\/li><\/ul>\n\n\n\n<p><strong>Memantine<\/strong><\/p>\n\n\n\n<ul><li>A different mechanism of action\nthan rivastigmine and others<\/li><li>It\u2019s a new NMDA receptor\nantagonist and related to amantadine<\/li><li>Known for slowing down of the\nprocess of dementia in moderate to severe dementia<\/li><li>MOA: Blocks the excitotoxic\nglutamate neurotransmitter competitively<\/li><li>Better tolerated than anti-ChEs<\/li><li>ADRs: constipation, tiredness,\nheadache, and drowsiness, etc.<\/li><\/ul>\n\n\n\n<p><strong>Piracetam<\/strong><\/p>\n\n\n\n<ul><li>Cyclic GABA derivative<\/li><li>The drug selectively improves the\nefficiency of higher telencephalic integrative activity<\/li><li>Piracetam taken with choline\n-synergistic effect that causes a greater improvement in memory<\/li><\/ul>\n\n\n\n<p>1.Enhanced efficacy of AMPA induced Ca2+ influx in brain cell<br>2.Increases the maximal density of AMPA receptors in synaptic membranes from rat cortex<br>3.Enhancement of learning and memory.<br>4.Facilitation of synaptic transmission &amp; inter-hemisphere information transfer.<br>5.Potentiates potassium-induced release of glutamate from rat hippocampal nerves<\/p>\n\n\n\n<p>\uf0d8 Not approved\nby US-FDA.<\/p>\n\n\n\n<p>\uf0d8 It is used in\nEurope, Asia &amp; South America.<\/p>\n\n\n\n<p><strong>Citicoline<\/strong><\/p>\n\n\n\n<ul><li>Chemically identical to\nCDP-choline, the natural precursor of the major cell membrane phospholipid\nphosphatidylcholine<\/li><li>enter the brain separately\n&amp;are used to resynthesize CDP-choline inside a brain cell<\/li><\/ul>\n\n\n\n<p><strong>Pyritinol(Pyrithioxine):-<\/strong><\/p>\n\n\n\n<ol><li>Improve regional blood flow<\/li><li>activate cerebral metabolism by\nselectively increasing glucose transport.<\/li><\/ol>\n\n\n\n<p><strong>Dihydroergotoxine\n(Codergocrine):-<\/strong><\/p>\n\n\n\n<p>Alpha-adrenergic blocker leading to increase\ncerebral blood flow<\/p>\n\n\n\n<ul><li>Evidence\nis poor for other approaches, including anti-amyloid therapies, antioxidants, estrogens\nand <em>Ginkgo biloba<\/em>, Brahmi, Ashwagandha<\/li><\/ul>\n\n\n\n<p><strong><em>Ginkgo biloba<\/em> <\/strong><strong>\u00e0 MOA:<\/strong><\/p>\n\n\n\n<ol><li>Restores impaired mitochondrial function &amp; improves neuronal energy supply<\/li><li>Improves compromised hippocampal neurogenesis &amp; neuroplasticity<\/li><li>Improves neurotransmission and increases dopamine levels in the prefrontal cortex (working memory &amp; executive control)<\/li><li>Inhibits aggregation &amp;toxicity of A\u03b2 protein, anti-inflammatory effects<\/li><li>Decreases blood viscosity &amp; enhances micro-perfusion, increasing cerebral blood flow<\/li><\/ol>\n\n\n\n<ul><li><strong>HuperzineA (HupA)<\/strong><ul><li><strong>AChE inhibitor &amp; NMDA receptor antagonist<\/strong> extracted from Huperzia serrata, a firmoss.<\/li><li>HupA used clinically to improve cognition and memory in AD and other forms of dementia in China.<\/li><li>Currently marketed as a memory-enhancing dietary supplement in the US.<\/li><li>In clinical trials, HupA demonstrable cognition-improving     capacity in AD patients <\/li><\/ul><\/li><\/ul>\n\n\n\n<ul><li><strong>Pioglitazone<\/strong><ul><li>Insulin sensitizer: thiazolidinedione -&gt; Peroxisome-Proliferator Activated Receptor \u03b3 (PPAR\u03b3) agonists.<\/li><li>It binds to PPAR\u03b3, affecting gene transcription and reducing inflammation<\/li><li>animal studies -&gt; a role in neuroinflammatory processes in AD and other neurodegenerative disorders<\/li><li>Phase II study \u00e0 evaluated the safety and tolerability of pioglitazone in patients with AD     \u00a0<\/li><\/ul><\/li><\/ul>\n\n\n\n<ul><li><strong>Genetic Modifications<\/strong> <ul><li>Genes in humans found that whose variations account for up     to 5% of memory performance<\/li><li>Genes for NMDA receptor &amp;adenylyl cyclase, genes involved in stages of the synaptic signal cascade<\/li><li>These obvious targets for enhancement<\/li><li>It has been proved in preclinical studies of rats and mice     \u00a0<\/li><\/ul><\/li><\/ul>\n\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Definition of Nootropic agents A drug that selectively improves the efficiency of higher telencephalic integrative activities by: Enhancement of learning and memory. Facilitation of synaptic transmission. Facilitates inter-hemisphere information transfer. Prevents the development of memory deficits. Increased tonic cortical control on subcortical areas. Cognition is defined as the processes an organism uses to organize information[&#8230;]\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/276"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=276"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/276\/revisions"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=276"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=276"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=276"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}