University:
Western Sydney University
Course:
MEDI 2003 | Clinical Sciences 2
Academic year:

2024
Views:

328

Pages:

2
Author:

Mariam A.

Drugs working on the serotonin system   Fenfluramine: stimulates release of 5-HT and blocks reuptake. o Clinical indications: for weight loss. o Discontinued because of side effects (e.g. heart valve disease, primary pulmonary hypertension). Fluoxetine: blocks reuptake  elevates 5-HT in the synapse. o Clinical indications: major depressive disorder. Glutamate  Major mediator of excitatory signals in the CNS.  Involved in most aspects of normal brain function, including cognition, memory and learning.  Interact with 4 receptor types: o NMDA receptor: controls Ca2+ channel (activation by glutamine requires glycine binding and displacement of magnesium ions). o AMPA receptor: controls Na+ channels. o Kainate receptor: controls Na+ channels. o Metabotropic glutamate receptor: coupled to G-proteins.  In excess, glutamate can lead to neuronal cell death (excitotoxicity). o Occurs as part of the ischaemic cascade and is associated with stroke and Alzheimer’s disease. o Ca2+ ions enter cells via NMDA receptor channels, leading to neuronal damage and eventual cell death. o Excessive intracellular Ca2+ damages mitochondria. o Glutamate/Ca2+ also promotes transcription factors for proapoptotic genes, or downregulation of transcription factors for anti-apoptotic genes. Gamma-aminobutyric acid (GABA)  Synthesised from glutamate.  Acts via 2 receptors: o GABAA (ionotropic): controls a Cl- channel. It contains 5 distinct binding sites, GABA site (direct agonist muscimol, direct antagonist bicuculline), benzodiazepine site (anxyiolytic drugs), barbiturates (anaesthetic, alcohol). o GABAB (metabotropic): controls K+ channel. Drugs working on the GABA system  Benzodiazepines: agonists of GABA receptors  enhance effect of GABA. o Results in sedative, hypnotic (sleep-inducing), anxiolytic (antianxiety), anticonvulsant, muscle relaxant and amnesic action. o Clinical indications: anxiety, insomnia, agitation, seizures, muscle spasms, alcohol withdrawal and as a premedication for medical or dental procedures.