Nurohumoral Transmission in the CNS.pptx

Nurohumoral Transmission in the CNS.pptx

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  PREPARED BY Prof. ASHISHN. UMALE M. PHARM IN PHARMACOLOGY ASSISTANT PROFESSOR SHRADDHA INSTITUTE OF PHARMACY, WASHIM- 444505 PHARMACOLOGY-I
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  Neurohumoral Transmission inCNS Neurohumoral transmission is the process by which nerve cells (neurons) communicate with each other using chemical substances called neurotransmitters. In the central nervous system (CNS), this communication takes place at specialized junctions known as synapses. In simple terms, when a neuron wants to send a message, it converts an electrical signal into a chemical signal. This chemical signal crosses a small gap between neurons and then again becomes an electrical signal in the next neuron, producing a response.
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  Steps of Neurotransmission Whenan electrical signal, called an action potential, reaches the nerve terminal, it triggers the release of neurotransmitters stored in synaptic vesicles. These neurotransmitters are released into the synaptic cleft (the gap between two neurons). They then diffuse across this gap and bind to specific receptors present on the postsynaptic neuron. This binding leads to the generation of a new electrical signal, which can either stimulate (excitatory) or suppress (inhibitory) the activity of the next neuron. Finally, the neurotransmitters are removed from the synaptic cleft either by reuptake into the presynaptic neuron or by enzymatic degradation. This step is important to terminate the signal and maintain proper balance in the CNS.
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  Types of Neurotransmittersin CNS Neurotransmitters in the CNS are broadly classified into two types based on their action. Excitatory neurotransmitters increase neuronal activity, while inhibitory neurotransmitters decrease neuronal activity. Proper brain function depends on a balance between these two types.
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  1. GABA (Gamma-AminobutyricAcid) GABA is the major inhibitory neurotransmitter in the CNS and is widely distributed in areas such as the cerebral cortex, cerebellum, and hippocampus. Its main function is to reduce excessive neuronal activity and maintain a calming effect on the brain. GABA is synthesized from glutamate by the enzyme glutamic acid decarboxylase (GAD) in the presence of vitamin B6. A deficiency of vitamin B6 can reduce GABA synthesis and may lead to seizures. GABA acts through two types of receptors: GABA-A and GABA-B. The GABA-A receptor is ionotropic and produces fast inhibition by allowing chloride ions to enter the neuron.
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  The GABA-B receptoris metabotropic and produces slower, prolonged inhibitory effects by affecting potassium and calcium channels. When GABA binds to its receptor, chloride ions enter the neuron, causing hyperpolarization. This makes the neuron less likely to generate an action potential. Pharmacologically, GABA is very important. Drugs like benzodiazepines (e.g., diazepam) and barbiturates enhance GABA activity and are used in anxiety, epilepsy, insomnia, and muscle spasms. Reduced GABA levels are associated with conditions like anxiety and epilepsy.
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  2. Glutamate Glutamate isthe principal excitatory neurotransmitter in the CNS and plays a major role in learning, memory, and synaptic plasticity. It is synthesized from glucose metabolism or from glutamine by the enzyme glutaminase. Glutamate acts on both ionotropic receptors (Faster) (NMDA, AMPA, and kainate) and metabotropic receptors (Slower) When glutamate binds to its receptors, it causes the influx of sodium and calcium ions into the neuron, leading to depolarization and excitation. Glutamate has important pharmacological roles. NMDA receptor antagonists such as ketamine and memantine are used in anesthesia and in conditions like Alzheimer’s disease. However, excessive glutamate activity can lead to excitotoxicity, where excessive calcium entry damages neurons. This is commonly seen in stroke, epilepsy, and neurodegenerative diseases.
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  3. Glycine Glycine isan inhibitory neurotransmitter mainly found in the spinal cord, brainstem, and retina. It plays an important role in motor control and reflex actions. It is synthesized from the amino acid serine. Glycine receptors are chloride ion channels similar to GABA-A receptors. When glycine binds to its receptors, chloride ions enter the neuron, causing inhibition through hyperpolarization ( - ve). Pharmacologically, glycine receptors are blocked by strychnine, which leads to severe convulsions due to loss of
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  Additionally, glycine actsas a co-agonist at NMDA receptors, assisting glutamate in excitatory transmission. Dysfunction of glycine may lead to muscle rigidity and spasticity.
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  4. Serotonin (5-HT) Serotoninis a monoamine neurotransmitter that regulates mood, sleep, appetite, pain perception, and behavior. It is synthesized from the amino acid tryptophan. Serotonin acts on multiple receptor types (5-HT1 to 5-HT7), most of which are G-protein coupled receptors. Its action may be excitatory or inhibitory depending on the receptor subtype, but it mainly acts as a modulatory neurotransmitter. Serotonin pathways originate from the raphe nuclei in the brainstem and project throughout the brain. Pharmacologically, selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and sertraline increase serotonin levels and are used to treat depression and anxiety disorders. Low serotonin levels are associated with depression, while excessive serotonin can lead to serotonin syndrome, characterized by agitation, hyperthermia, and confusion.
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  5. Dopamine Dopamine isa catecholamine neurotransmitter involved in movement, reward, cognition, and hormonal regulation. It is synthesized from the amino acid tyrosine via L-DOPA. Dopamine acts on D1-like (excitatory) and D2-like (inhibitory) receptors. Dopamine functions through four major pathways in the brain: the nigrostriatal pathway (movement control), mesolimbic pathway (reward and pleasure), mesocortical pathway (cognition and emotion), and tuberoinfundibular pathway (hormonal regulation). Pharmacologically, levodopa is used to increase dopamine levels in Parkinson’s disease, while antipsychotic drugs like haloperidol block dopamine receptors. A deficiency of dopamine leads to Parkinson’s disease, characterized by tremors and rigidity, while excess dopamine activity is associated with schizophrenia.