Section 10 (PT2) - Drugs and Toxins Affecting the CNS

Click to edit Master title style Click to edit Master text styles Second level Third level Fourth level Fifth level Click to edit Master title style Click to edit Master text styles Second level Third level Fourth level Fifth level Principles of Pharmacology and Toxicology (BIOL3020) Section 10 Drugs Affecting the Central Nervous System (Part II) Rang et al 2007 (Chapters 32-34) Stine and Brown (2006) Principles of Toxicology Gamma-aminobutyric acid (GABA) Gamma-aminobutyric acid (GABA) Gamma-aminobutyric acid (GABA) receptors GABA acts on two distinct types of receptors GABAA-receptor is a ligand-gated chloride channel GABAB-receptor is a G-protein-coupled receptor Both are inhibitory  GPCR G-Protein GABAA GABAB Hyperpolarization (-) Gamma-aminobutyric acid (GABA) receptors What is the mechanism of GABAB inhibition G-Protein GABAB The GABAA Receptor U  Agonists that interact with GABAA receptors v  Benzodiazepine action Increases the affinity of GABA for receptor No effect on glutamate or glycine channels Antagonists that interact with GABAA receptors Glycine and Glycine Receptors  Other CNS neurotransmitters  Other CNS neurotransmitters Serotonin Biosynthesis 5-HT (serotonin) 5-Hydroxytryptamine 5-HT is present in diet but most is metabolized before entering the blood stream Most arises from biosynthesis Tryptophan is converted into 5-hydroxytrophan Then 5-hydroxytriptamine 5-HT Receptors 5-HT1 Agonists used to treat anxiety (buspirone) Agonist for some receptors used to treat migraines (sumatriptan) 5-HT2 Antagonists used to treat migraines (Methysergide) Targets for hallucinogenic drugs (LSD) which act as agonists 5-HT3 Excitatory effect ligand-gated cation channel Antagonists are used to treat nausea Example-Ondansetron 5-HT4 Effect presynaptic neurons affecting ACh release increase cognition  SSRIs Serotonin SSRI Serotonin transporter Serotonin Receptor Serotonin neuron Other neurotransmitters include Noradrenaline Acetylcholine Histamine  Other CNS neurotransmitters Are small, non-polar and able to pass though the blood-brain barrier. CNS is low in detoxifying enzymes such as p450 Note The blood-brain barrier is not well developed at birth and provides less protection in infants Effect of Toxins on CNS