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Neurotransmission and the CNS BY PROF. Azza El-Medany Neurotransmitters • Exert their effect by binding to specific receptors on the neuronal postsynaptic membranes. • They can either excite the neurons → increase their activity or inhibit the neurons → suppressing their activity. What is the importance of understanding neurotransmitters To understand the etiology of diseases To suggest the best drugs to be used To understand the other clinical uses of any particular drug Examples of some neurotransmitters & their relation to diseases • Acetylc holine • Type of receptors : Muscarinic receptors Nicotinic receptors Role of Acetylcholine in the CNS • Ach is thought to be involved in cognitive functions such as : memory , arousal and attention. It plays a role in the enhancement of sensory perception when we wake up . • Damage of cholinergic pathways is associated with memory deficits associated with Alzheimer,s disease. Continue • Treatment of Alzheimer,s disease involved the use of directly & indirectly acting cholinomimetic drugs. • Increase brain level of Ach predispose to parkinson,s disease. Mood Disorders and Neurotransmitters • Norepinephrine ( NEF ) : • Increase norepinephrine release tend to increase excitatory activity within the brain → Mania • Treatment : Drugs that decrease NEF e.g. neuroleptic drugs NEF ( continue ) • Decrease of NEF brain level→ Depression • Treatment : Drugs that increase NEF e.g. Tricyclic antidepressant drugs Serotonin • Although the CNS contains less than 2% of the total serotonin in the body, serotonin plays a very important role in a range of brain functions including : • Mood control • Regulation of sleep • Pain perception • Body temperature Serotonin( continue ) • Blood pressure • Hormonal activity Diseases that influenced by serotonin ( 5-HT) level • • • • • • Affective Disorders or Bipolar disorders Schizophrenia Obsessive Compulsive Disorders Generalized Anxiety Depression Premenstrual dysphoric disorder Continue • Outside the brain , serotonin exerts a number of important effects , involving gastrointestinal & cardiovascular systems Dopamine • Monoamine neurotransmitter, concentrated in very specific groups of neurons called basal ganglia. • Three important pathways throughout the brain : • Nigrostriatal • Mesolimbic • Tuberoinfundibular Continue • ↑ of dopamine levels in brain has a role in the development of schizophrenia Treatment by blocking dopamine receptors by neuroleptic drugs . • ↓ of dopamine levels is a contributing factor in parkinson,s disease . Treatment by increasing dopamine content. GABA & Glutamate Transmitters • Decrease in GABA levels ( an inhibitory neurotransmitters ) or increase in glutamate ( an excitatory neurotransmitters ) • Predispose to epilepsy Treatment by antiepileptic drugs Conclusion • Understanding the numerous neurotransmitters , their receptors , location and interaction with one another has been central to the design of medicines for mental illness. • This acquired knowledge has led to the development of successful products for many brain disorders including depression, anxiety, sc hizophrenia, parkinson,s disease & epilepsy. Continue • Combinations of centrally acting drugs are frequently given to therapeutic advantages e.g. an anticholinergic drug & levodopa in for parkinson,s disease