University:
West Coast University
Course:
PHAR 835 | IPC Neurology/Psychiatry
Academic year:

2024
Views:

214

Pages:

10
Author:

Asal A.

Glutamate Pharmacology Dementia Treatment Supplemental Guidance to Handout and Reading Assignment Basic & Clinical Pharmacology, 16e Bertram G. Katzung, Todd W. Vandera. Chapter 7 Parto Khansari Ph.D. 8/21/2024 11-12:30 Drugs List Glutamatergic Pathways me The most abundant excitatory neurotransmitter the CNS. Associated with motor neuron activation, pain sensation (hyperalgesia) and certain types of memory formation. 87130 Overstimulation of glutamate release or activation of glutamate receptors is referred to as Excitotoxicity implicated as a pathophysiologic mechanism in many diseases, including stroke and trauma, hyperalgesia, epilepsy and neurodegenerative syndromes such as Huntington’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis (ALS). Glutamate Synthesis Two distinct pathway to synthesis glutamates: 1. α-ketoglutarate formed in the Krebs cycle is transaminated to glutamate in neurons 2. glutamine produced and secreted by glial cells is transported into nerve terminals and converted to glutamate by glutaminase Glutamate Receptors EM Ionotropic glutamate receptors: • Fast excitatory synaptic responses. • Gated ion channels that allow the flow of Na+, K+, and, Ca2+ ions across plasma membranes • AMPA, kainate, and NMDA receptors Z Metabotropic glutamate receptors (mGluR) : • Slow responses • G proteins Coupled Receptors (GPCR) • Three groups (I, II, and III) according to its sequence homology, signal transduction mechanism, and pharmacology Glutamate Receptors Type Subtype Agonist Action Location located throughout the CNS, particularly in the hippocampus and cerebral cortex located throughout the CNS, particularly in the hippocampus and cerebral cortex Memory or e expressed primarily in the hippocampus, cerebral cortex, and spinal cord NMDA Receptor NMDA receptors differ from the other ionotropic glutamate receptors in two important respects—they require the binding of multiple ligands for channel activation, and their gating depends on more intense presynaptic activity than that required to open AMPA or kainate receptors. weneedglycinezinc mug for catogetin Alzheimer Disease Pathology Some processes involved in Alzheimer disease. From the left: Mitochondrial dysfunction, possibly involving glucose utilization; synthesis of protein tau and aggregation in filamentous tangles; synthesis of amyloid beta (Aβ) and secretion into the extracellular space, where it may interfere with synaptic signaling and accumulates in plaques. (Reproduced with permission from Roberson ED, Mucke L: 100 years and counting: prospects for defeating Alzheimer’s disease, Science 2006 Nov 3;314(5800):781-784.) Citation: Chapter 60 Special Aspects of Geriatric Pharmacology, Katzung BG, Vanderah TW. Basic & Clinical Pharmacology, 15e; 2021. Available at: https://accesspharmacy.mhmedical.com/content.aspx?sectionid=250604555&bookid=2988 Accessed: September 04, 2023 Copyright © 2023 McGraw-Hill Education. All rights reserved Dementia just know NMDAplagea notein deena • AD is the most common cause of dementia • Hallmark of AD are deposition of the β-amyloid peptide (Aβ) and tau protein neurofibrillary tangles • AD typically begins in temporal lobe, spreads to the hippocampus and other limbic structures, and eventually causing a more widespread degeneration. • NMDA (N-methyl-D-aspartate) receptor-dependent longterm potentiation (LTP) and long-term depression (LTD) of excitatory neurons, such as hippocampal neurons are associated with learning and memory. • Memantine is a noncompetitive NMDA receptor antagonist (channel blocker) and used in the treatment of AD. specificNMDA G Dementia Elevated ACh levels during wakefulness appear to benefit memory encoding processes. Acetylcholinesterase rapidly degrades ACh in the synaptic cleft. Donepezil is a cholinesterase inhibitor and used in the treatment of AD.