Week 4: Overview of Central Nervous System Pharmacology
Week 4, Module 1 Objectives:
1. Explain the differences between voltage-gated and ligand-gated ion channels.
2. Identify the major excitatory and inhibitory CNS neurotransmitters in the CNS.
3. Identify the sites of drug action at synapses and the mechanisms by which drugs modulate synaptic
transmission.
,Chapter 18: Introduction to Central Nervous System Pharmacology
Central Nervous System (CNS) Drugs
● Agents that act on the brain and spinal cord
● Medical uses
➢ Relief of pain
➢ Suppression of seizures
➢ Production of anesthesia
➢ Treatment of psychiatric disorders
● Nonmedical uses
➢ Stimulant, depressant, euphoriant, and other “mind-altering” abilities
Transmitters of the CNS
● Peripheral nervous system: Acetylcholine, norepinephrine, and epinephrine
● CNS: At least 21 compounds
● Evidence supports a neurotransmitter role for dopamine, norepinephrine, serotonin, and enkephalins
The Blood-Brain Barrier
● Impedes entry of drugs into the brain
➢ Passage across the blood-brain barrier limited to lipid-soluble drugs
➢ Protein-bound or highly ionized drugs cannot cross
How CNS Drugs Produce Therapeutic Effects
● Precise mechanism versus plausible hypotheses
● We do not fully understand the brain in either health or disease
● Although we cannot state with certainty how CNS drugs act, we do have sufficient data to permit the
formulation of plausible hypotheses
Adaptation of the CNS to Prolonged Drug Exposure
● Different effects possible when drug is taken chronically versus the initial use of the drug
● Increased therapeutic effects
● Certain drugs used in psychiatry (such as antipsychotics or antidepressants) must be taken for several
weeks before full therapeutic effects develop
● Beneficial responses may be delayed because they result from adaptive changes and not from the
direct effects of drugs on synaptic function
, ● Full therapeutic effects are not seen until the CNS has had time to modify itself in response to
prolonged drug exposure
● Decreased side effects: When CNS drugs are taken chronically, the intensity of the side effects may
decrease, but the therapeutic effects remain undiminished
● Example:
➢ Morphine is taken to control pain
➢ Nausea is a common side effect early on
➢ Treatment continues, nausea diminishes, and analgesic effects persist
● Tolerance
➢ Decreased response occurring during the course of prolonged drug use
● Physical dependence
➢ State in which abrupt discontinuation of drug use will precipitate a withdrawal syndrome
Development of New Psychotherapeutic Drugs
● Complexity of mental health
● Lack of adequate animal models of mental illness
● Mentally healthy individuals cannot be used as subjects
➢ No effect or paradoxical effects
➢ Psychopharmacologic accidental discoveries
● The process:
➢ Structural analogs synthesized
➢ Biochemical and physiologic screening tests
➢ Serious toxicity ruled out and then drugs tested in humans
➢ Small advances versus major therapeutic breakthroughs
Approaching the Study of CNS Drugs
● Recognize the following:
➢ There are numerous neurotransmitters
➢ Their precise functional roles are not clear
➢ Their complexity makes it difficult to know with certainty just how CNS drugs produce their
effects
, Chapter 19: Drugs for Parkinson Disease
Parkinson Disease
● Parkinson disease (PD) is a neurodegenerative disorder of the extrapyramidal system associated with
the disruption of neurotransmission in the striatum
➢ Characterized by dyskinesias and akinesia
➢ Proper function of the striatum requires a balance between the neurotransmitters dopamine
and acetylcholine (ACh)
➢ Imbalance between dopamine and ACh results from the degeneration of the neurons that
supply dopamine to the striatum
● Affects more than 1 million Americans
● Second only to Alzheimer disease as the most common degenerative disease of the neurons
● Symptoms generally appear during middle age and progress
● No cure for motor symptoms
● Drug therapy can maintain functional mobility for years (i.e., prolongs/improves quality of life)
Cardinal Symptoms of PD
● Dyskinesias
➢ Tremor at rest
➢ Rigidity
➢ Postural instability
➢ Bradykinesia (slowed movement)
➢ Tremor
● In addition to motor symptoms
➢ Autonomic disturbances
➢ Depression
➢ Psychosis and dementia
Dopamine/ACh Imbalance in Striatum
● Imbalance results from degeneration of the neurons that supply dopamine to the striatum
● Without adequate dopamine, ACh causes excessive stimulation of neurons that release
gamma-aminobutyric acid
● Overactivity of gamma-aminobutyric acid neurons contributes to the motor symptoms of PD
● Uncertainty regarding the cause of degeneration; may be alpha-synuclein
Week 4, Module 1 Objectives:
1. Explain the differences between voltage-gated and ligand-gated ion channels.
2. Identify the major excitatory and inhibitory CNS neurotransmitters in the CNS.
3. Identify the sites of drug action at synapses and the mechanisms by which drugs modulate synaptic
transmission.
,Chapter 18: Introduction to Central Nervous System Pharmacology
Central Nervous System (CNS) Drugs
● Agents that act on the brain and spinal cord
● Medical uses
➢ Relief of pain
➢ Suppression of seizures
➢ Production of anesthesia
➢ Treatment of psychiatric disorders
● Nonmedical uses
➢ Stimulant, depressant, euphoriant, and other “mind-altering” abilities
Transmitters of the CNS
● Peripheral nervous system: Acetylcholine, norepinephrine, and epinephrine
● CNS: At least 21 compounds
● Evidence supports a neurotransmitter role for dopamine, norepinephrine, serotonin, and enkephalins
The Blood-Brain Barrier
● Impedes entry of drugs into the brain
➢ Passage across the blood-brain barrier limited to lipid-soluble drugs
➢ Protein-bound or highly ionized drugs cannot cross
How CNS Drugs Produce Therapeutic Effects
● Precise mechanism versus plausible hypotheses
● We do not fully understand the brain in either health or disease
● Although we cannot state with certainty how CNS drugs act, we do have sufficient data to permit the
formulation of plausible hypotheses
Adaptation of the CNS to Prolonged Drug Exposure
● Different effects possible when drug is taken chronically versus the initial use of the drug
● Increased therapeutic effects
● Certain drugs used in psychiatry (such as antipsychotics or antidepressants) must be taken for several
weeks before full therapeutic effects develop
● Beneficial responses may be delayed because they result from adaptive changes and not from the
direct effects of drugs on synaptic function
, ● Full therapeutic effects are not seen until the CNS has had time to modify itself in response to
prolonged drug exposure
● Decreased side effects: When CNS drugs are taken chronically, the intensity of the side effects may
decrease, but the therapeutic effects remain undiminished
● Example:
➢ Morphine is taken to control pain
➢ Nausea is a common side effect early on
➢ Treatment continues, nausea diminishes, and analgesic effects persist
● Tolerance
➢ Decreased response occurring during the course of prolonged drug use
● Physical dependence
➢ State in which abrupt discontinuation of drug use will precipitate a withdrawal syndrome
Development of New Psychotherapeutic Drugs
● Complexity of mental health
● Lack of adequate animal models of mental illness
● Mentally healthy individuals cannot be used as subjects
➢ No effect or paradoxical effects
➢ Psychopharmacologic accidental discoveries
● The process:
➢ Structural analogs synthesized
➢ Biochemical and physiologic screening tests
➢ Serious toxicity ruled out and then drugs tested in humans
➢ Small advances versus major therapeutic breakthroughs
Approaching the Study of CNS Drugs
● Recognize the following:
➢ There are numerous neurotransmitters
➢ Their precise functional roles are not clear
➢ Their complexity makes it difficult to know with certainty just how CNS drugs produce their
effects
, Chapter 19: Drugs for Parkinson Disease
Parkinson Disease
● Parkinson disease (PD) is a neurodegenerative disorder of the extrapyramidal system associated with
the disruption of neurotransmission in the striatum
➢ Characterized by dyskinesias and akinesia
➢ Proper function of the striatum requires a balance between the neurotransmitters dopamine
and acetylcholine (ACh)
➢ Imbalance between dopamine and ACh results from the degeneration of the neurons that
supply dopamine to the striatum
● Affects more than 1 million Americans
● Second only to Alzheimer disease as the most common degenerative disease of the neurons
● Symptoms generally appear during middle age and progress
● No cure for motor symptoms
● Drug therapy can maintain functional mobility for years (i.e., prolongs/improves quality of life)
Cardinal Symptoms of PD
● Dyskinesias
➢ Tremor at rest
➢ Rigidity
➢ Postural instability
➢ Bradykinesia (slowed movement)
➢ Tremor
● In addition to motor symptoms
➢ Autonomic disturbances
➢ Depression
➢ Psychosis and dementia
Dopamine/ACh Imbalance in Striatum
● Imbalance results from degeneration of the neurons that supply dopamine to the striatum
● Without adequate dopamine, ACh causes excessive stimulation of neurons that release
gamma-aminobutyric acid
● Overactivity of gamma-aminobutyric acid neurons contributes to the motor symptoms of PD
● Uncertainty regarding the cause of degeneration; may be alpha-synuclein
