Lecture5_neuropharmacology - Neuropharmacology What are...

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Neuropharmacology
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What are neurotransmitters? Chemicals released by neurons to send messages to other neurons There are hundreds (or perhaps even thousands) of different substances that can function as neurotransmitters in the brain (why so many??!!) What are the defining characteristics of “neurotransmitters” that distinguish them from other brain chemicals? Specific machinery for synthesizing (making) the chemical in neurons. Packaged into vesicles. Release is coupled to membrane voltage (e.g., action potentials). Specific and selective post-synaptic receptors on target neurons. Mechanisms for inactivating the transmitter after it has bound its receptor. It was once believed that each neuron in the brain released only ONE neurotransmitter substance. We now know this is false (some neurons release several transmitters).
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Chemical Communication Systems
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What are receptors? Protein complexes embedded in the membranes of neurons which bind neurotransmitters (the transmitters are usually released by other neurons, but sometimes by themselves!) When neurotransmitter binds to a neuron’s receptors, it causes some physiological or chemical response in the neuron Two major categories of receptors: Ionotropic receptors (ligand-gated ion channels) Metabotropic receptors (G-protein coupled receptors)
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Endogenous vs Exogenous Ligands Endogenous ligands of a receptor are chemicals normally found in the body which bind to the receptor Exogenous ligands of a receptor are compounds not found in the body that, when introduced into the body, can affect the receptor in one of two ways: Agonists bind to the receptor and activate it in much the same way as its normal endogenous ligands (sometimes even more so) Antagonists bind to the receptor and prevent it from being activated by its normal endogenous ligand Many drugs that affect our minds and bodies are exogenous ligands for neurotransmitter receptors!
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Blood-Brain Barrier The brain is supplied with oxygen and nourishment by a network of blood vessels (capillaries) that permeate the entire brain The capillary walls are formed by endothelial cells that form tight junctions with one another Surrounding the capillary walls are “foot process” from astrocytes that form a tight seal around the capillary Most molecules cannot cross the BBB from the bloodstream to the brain (CSF) There are two ways to get across: Passive diffusion (water, gases, small fat soluble molecules) Active transport (glucose, amino acids, some hormones & peptides)
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Catecholamines Norepinephrine (noradrenalin) is synthesized from dopamine by dopamine b -hydroxylase Epinephrine (adrenalin) is synthesized from norepinephrine by phenylethanolamine-N- methyltransferase Catecholamines are neurotransmitters that are synthesized from the amino acid tyrosine: Dopamine Norepineprhine (Noradrenalin) Epinephrin (Adrenalin) Tyrosine is catalyzed into Levadopa (or L-DOPA) by tyrosine hydroxylase , and L-DOPA is then converted into dopamine by amino acid decarboxylase
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