Lect 6

• DRUGS Acting on the Central Nervous System (CNS) Lecture 12: CNS Drugs, Introduction Anait S Levenson, M.D., Ph.D
• GPCRs are 7 transmembrane helixes, also known as 7-transmembrane receptors, 7TM-R.
• GPCRs regulate sensory (taste, light, smell) and non-sensory (neurological and endocrine) signals.
• Each receptor binds to its ligand, causing conformational changes.
• Structure of GPCRs involves 7 transmembrane alpha helixes receptors interacting with trimetic signal-transducing G-proteins.
• G-proteins consist of α, β, and γ subunits.
• No receptor is needed for CPCRs as they are the main targets of existing drugs, with 30-50% of drugs binding to them.
• α separates from β and γ, and they interact with other proteins.
• 2nd messengers (cAMP) act on heart, muscle, vessels.
• GPCRs detect molecules outside the cells and activate cellular responses.
• GPCRs comprise the largest family of transmembrane receptors, with around 1000 in humans.
• Sodium Na+; potassium K+; chloride Cl-; organic anions A-; organic cations A+.
• Electrical synapses use gap junction proteins.
• Cal messengers are released from presynaptic neurons to allow them to communicate with neighboring cells.
• Neurons maintain different concentrations of certain ions (sodium (Na+) and potassium (K+)) across their cell membranes.
• APs are one-directional (from the cell body to axon terminal) and are all-or-nothing (on-off switches).
• Action potential: + inside; - outside: channels are open.
• The process of communication occurs via orchestrated chemical (release of neurotransmitters) and electrical (alteration of neuronal membrane potential) actions.
• Action potentials (APs) are electrical signals carried along neurons.
• Synapses are junctions that allow signals to pass.
• The receptor on the neighboring cell is responsible for receiving the message.
• Propagation of Action Potential: Membrane potential: the differences between inside and outside of the cell.
• Electrical and Chemical Synapses use ligand-gated ion proteins, G-protein coupled receptors, voltage-gated ion channels, and gap junction proteins.
• Action potential (AP), nerve impulse: the change in electrical potential (voltage) associated with the passage of an impulse along the membrane of a neuron.
• Ligand-gated ion proteins are very fast, hard to control, but can be controlled.
• Resting potential: - inside; + outside: channels are closed.
• Impulse is generated through the flow of positively charged ions across the neuronal membrane.
• Voltage-gated ion channels are controlled (NT).
• Chemical synapses use ionotropic receptors (ligand-gated ion proteins) and metabotropic receptors (G-protein coupled proteins).
• CNS acting drugs have a major therapeutic/clinical and mental (psychological) importance.
• CNS agents are medicines that affect the Central Nervous System (CNS).
• Drugs mimic NTs.
• CNS drugs affect the brain’s use and output of neurotransmitters (NT).
• The Enteric Nervous System (ENS) functions in a "Feed - or - Breed" mode during rest, a "Rest - and - Digest" mode during relaxation, and a "Fight - or - flight" mode during stress.
• Neurons communicate through synapses or neuronal junctions.
• Drugs speed up the production of NTs.
• The Central Nervous System (CNS) consists of the Brain (CNS), Spinal Cord (CNS), Peripheral Nervous System (PNS), Autonomic Nervous System (ANS), Enteric Nervous System (ENS).
• The Peripheral Nervous System (PNS) conveys information from the Central Nervous System (CNS) to smooth muscle, cardiac muscle, and glands.
• Glial cells or neuroglia provide support functions such as Astrocytes, Oligodendrocytes, Microglial cells, Ependymal cells.
• Neurotransmitters (NT) are the chemicals used in this communication.