9.3 Characteristics of Drugs to Treat Nervous System Disorders

Neurotransmitters are chemical messengers that allow our nervous system to function. They play crucial roles in everything from muscle movement to mood regulation. Understanding how these chemicals work is key to grasping how drugs affect our bodies and minds.

Drugs can interact with our nervous system in various ways. Some mimic or block neurotransmitters, while others affect their release or reuptake. This knowledge helps us comprehend how medications treat conditions like depression, anxiety, and Parkinson's disease.

Neurotransmitters and Nervous System Pharmacology

Neurotransmitters and their functions

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• Acetylcholine (ACh)
  • Serves as a neurotransmitter in both the central nervous system (CNS) and peripheral nervous system (PNS)
  • Plays a crucial role in memory formation, learning processes, and muscle contraction (skeletal and smooth muscle)
  • Involved in the regulation of autonomic functions such as heart rate, digestion, and secretion
• Norepinephrine (NE)
  • Acts as a neurotransmitter primarily in the sympathetic nervous system
  • Increases heart rate, blood pressure, and blood glucose levels during stress or physical activity
  • Plays a key role in the body's "fight or flight" response to prepare for action in emergency situations
• Dopamine (DA)
  • Functions as a neurotransmitter in the CNS, particularly in the brain's reward and motor control systems
  • Regulates movement, emotional responses, motivation, and feelings of pleasure and reward
  • Imbalances in dopamine levels are associated with neurological disorders such as Parkinson's disease and psychiatric conditions like schizophrenia
• Serotonin (5-HT)
  • Serves as a neurotransmitter in the CNS and gastrointestinal tract
  • Regulates mood, sleep patterns, appetite, and pain perception
  • Dysregulation of serotonin is linked to various psychiatric disorders, including depression and anxiety
• ###Gamma-aminobutyric_acid_(GABA)_0###
  • Acts as the primary inhibitory neurotransmitter in the CNS
  • Reduces neuronal excitability by hyperpolarizing the postsynaptic membrane
  • Plays a crucial role in regulating anxiety levels and promoting relaxation
• Glutamate
  • Serves as the primary excitatory neurotransmitter in the CNS
  • Involved in learning, memory formation, and synaptic plasticity (the ability of synapses to strengthen or weaken over time)
  • Excessive glutamate activity can lead to excitotoxicity, which is associated with neurodegenerative disorders

Drug interactions with autonomic receptors

• Cholinergic receptors
  • Muscarinic receptors (M1-M5)
    • Activated by ACh and targeted by drugs like atropine and scopolamine to block their effects
    • Used to treat conditions such as motion sickness, overactive bladder, and chronic obstructive pulmonary disease (COPD)
  • Nicotinic receptors (NM, NN)
    • Activated by ACh and targeted by drugs like nicotine and varenicline to stimulate or partially activate these receptors
    • Used to treat conditions such as smoking cessation and Alzheimer's disease by improving cognitive function
• Adrenergic receptors
  • Alpha-1 receptors (α1)
    • Activated by NE and targeted by drugs like prazosin and tamsulosin to block their effects
    • Used to treat conditions such as hypertension and benign prostatic hyperplasia by relaxing smooth muscle
  • Alpha-2 receptors (α2)
    • Activated by NE and targeted by drugs like clonidine and guanfacine to stimulate these receptors
    • Used to treat conditions such as hypertension and attention deficit hyperactivity disorder (ADHD) by reducing sympathetic activity
  • Beta-1 receptors (β1)
    • Activated by NE and targeted by drugs like atenolol and metoprolol to block their effects
    • Used to treat conditions such as hypertension, angina, and heart failure by reducing heart rate and contractility
  • Beta-2 receptors (β2)
    • Activated by NE and targeted by drugs like albuterol and salmeterol to stimulate these receptors
    • Used to treat conditions such as asthma and COPD by promoting bronchodilation

Sympathetic vs parasympathetic nervous system agents

• Sympathetic nervous system (SNS) stimulants
  • Drugs that increase the activity of the SNS by mimicking or enhancing the effects of NE
  • Examples include epinephrine, norepinephrine, and amphetamines
  • Used to treat conditions such as anaphylaxis, cardiac arrest, and narcolepsy by increasing alertness and cardiovascular function
• Sympathetic nervous system (SNS) blockers
  • Drugs that decrease the activity of the SNS by blocking the effects of NE at adrenergic receptors
  • Examples include alpha blockers (prazosin) and beta blockers (propranolol)
  • Used to treat conditions such as hypertension, angina, and migraine by reducing peripheral resistance and heart rate
• Parasympathetic nervous system (PNS) stimulants
  • Drugs that increase the activity of the PNS by mimicking or enhancing the effects of ACh
  • Examples include pilocarpine and bethanechol
  • Used to treat conditions such as glaucoma and urinary retention by promoting smooth muscle contraction and secretion
• Parasympathetic nervous system (PNS) blockers
  • Drugs that decrease the activity of the PNS by blocking the effects of ACh at muscarinic receptors
  • Examples include atropine, scopolamine, and glycopyrrolate
  • Used to treat conditions such as bradycardia, overactive bladder, and COPD by reducing smooth muscle tone and secretion

Drug mechanisms and nervous system interactions

• Blood-brain barrier
  • Selective permeability barrier that separates the circulating blood from the brain extracellular fluid
  • Influences drug delivery to the CNS and must be considered when developing CNS-active medications
• Neurotransmitter reuptake
  • Process by which neurotransmitters are removed from the synaptic cleft
  • Target of many antidepressants and other psychoactive drugs to prolong neurotransmitter effects
• Synaptic transmission
  • Process of signal transmission between neurons at synapses
  • Affected by various drugs to modulate nervous system function
• Receptor agonists and antagonists
  • Agonists: Drugs that activate specific receptors to mimic or enhance neurotransmitter effects
  • Antagonists: Drugs that block specific receptors to inhibit neurotransmitter effects
• Neuroplasticity
  • The brain's ability to form new neural connections and adapt in response to experiences or injury
  • Influenced by certain medications and therapies to promote recovery or manage neurological conditions