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Drug Actions in The Nervous System

Drug Actions in The Nervous System . Lecture Outline. Neurons and Membrane Potentials Synaptic Processes and Drug Actions at Synapses Nervous System Organization and Key Structures Neurochemical Pathways and Key Examples Specific Examples of Synaptic Actions of Drugs. Neurons.

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Drug Actions in The Nervous System

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  1. Drug Actions in The Nervous System

  2. Lecture Outline • Neurons and Membrane Potentials • Synaptic Processes and Drug Actions at Synapses • Nervous System Organization and Key Structures • Neurochemical Pathways and Key Examples • Specific Examples of Synaptic Actions of Drugs

  3. Neurons • Nervous systems consist of specialized cells (neurons) for receiving, integrating and transmitting information.

  4. Neuron Cell Membranes • Membrane Structure • Semipermeable phospholipid bilayer • Proteins • Ion channels • Transport pumps • Receptors

  5. Membrane Potential

  6. Resting Membrane Potential • Due to an uneven distribution of ions inside and outside the cell membrane • more positively charged ions outside, more negatively charged ions inside • The ions responsible for the membrane potential include • K+, Na+, Cl-, Ca2+ and some large molecules of amino acids • Two processes regarding ion movement • Diffusion • Electrostatic charges • Membranes are not permeable to ions • specialized channels (ionophores)

  7. Action Potential • Depolarization • Hyperpolarization • Threshold • Voltage-gated ion channels

  8. Postsynaptic Potential • Graded Potentials • Postsynaptic Potentials • Excitatory (EPSP) • Inhibitory (IPSP)

  9. Neurochemical Synapse • Presynaptic Membrane • Postsynaptic Membrane • Synaptic Vesicles • Synaptic Cleft • Receptor Sites

  10. Chemical Messengers • Hormones: released from endocrine glands, widespread targets. • Neurotransmitters: released from neurons, discrete and local targets. • Receptors: Cell structures that receive chemical messages, including those from hormones and neurotransmitters.

  11. Major Steps in Neurochemical Synaptic Transmission • Synthesis • Storage • Neurotransmitter Release • Receptor Activation • Deactivation • Enzymatic Deactivation • Reuptake

  12. Synthesis

  13. Receptor Activation • Ionotropic Receptors • Involve ligand-gated ion channels • Metabotropic Receptors • Stimulate a cascade of events involving G proteins and second messengers • interact with gated ion channels • activate kinases, which may influence transcription factors and gene expression

  14. Drug-Receptor Interactions

  15. Drug-Receptor Interactions • Agonists • Competitive • Noncompetitive • Antagonists • Competitive • Noncompetitive

  16. Neuropharmacology • The study of drug actions on neurochemical and neurophysiological processes. • Drugs are exogenous ligands. • Drugs may activate the same receptors as the endogenous ligands (neurotransmitters). • Drugs may modify the actions of endogenous ligands.

  17. Nervous System Divisions • The Central Nervous System • Brain and Spinal Cord • Somatic Nervous System • Sensory Nerves (inputs, afferents) • Motor Nerves (outputs, efferents) • The Autonomic Nervous System (ANS) • Sympathetic • Parasympathetic

  18. NERVOUS SYSTEM DIVISIONS

  19. Autonomic Nervous System • Controls body’s internal environment • Regulates involuntary functions of the body • Divisions • Sympathetic • Parasympathetic • Many psychoactive drugs simultaneously affect CNS and ANS

  20. Autonomic Nervous System

  21. Parasympathetic Division Exits Cranial and Sacral regions of SC Acetylcholine in postganglionic synapses Energy Conservation Decreased hr, bp Pupil constriction Salivation Gastric Secretion Sympathetic Division Exits Thoracic-Lumbar region of SC Norepinephrine in postganglionic synapses Fight-or-Flight Response Elevated hr, bp Pupil dilation Increased sweat gland activity Dry mouth Increased blood flow to muscles Autonomic Nervous System

  22. NEUROTRANSMITTERS IN THE BRAIN • Chemical Pathways • Dopamine • Most widely studied neurobiological theory of drug dependence relates to dopamine • Acetylcholine • Reduced quantities found in Alzheimer’s patients • Norepinephrine • Stimulant drugs may induce wakefulness through these pathways

  23. NEUROTRANSMITTERS IN THE BRAIN • Chemical Pathways • Serotonin • Research on weight control, aggressiveness, and depression are centered on these chemicals • GABA • Widespread in CNS • GABA dysfunction associated with seizure disorders • Anticonvulsants are GABA agonists • Endorphins • Involved in body’s natural mechanisms of pain relief • Other functions not well understood

  24. Neurochemical Pathways in CNS Acetylcholine (ACh) Dopamine (DA) Norepinephrine (NE) Serotonin (5-HT)

  25. DRUG ACTIONS IN THE BRAIN • Possible Mechanisms of Drug Actions • Effects of all neurons • Some drugs (e.g., alcohol) can affect all neurons • Effects on Specific Neurotransmitter Systems • Different psychoactive drugs produce different types of effects on neurochemical transmission and on different neurotransmitter systems

  26. SOME PRESYNAPTIC DRUG ACTIONS

  27. SOME POSTSYNAPTIC DRUG ACTIONS

  28. Neurotransmitter type of effect CNS changes drugs of abuse dopamine GABA serotonin acetylcholine endorphins inhibitory- excitatory inhibitory inhibitory excitatory- inhibitory inhibitory euphoria agitation paranoia sedation relaxation drowsiness depression sleep relaxation sedation mild euphoria excitation insomnia mild euphoria block pain slow respiration amphetamines, cocaine alcohol, Valium-type barbiturates LSD tobacco, nicotine narcotics Common Neurotransmitters and Drug Actions

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