Table of Contents
Overview – Nervous System Drug Targets
Nervous system drug targets span the afferent, efferent, and autonomic pathways. They include peripheral and central mechanisms involved in pain modulation, neurotransmitter signalling, and motor or autonomic control. This article outlines key pharmacological interventions acting on TRPV1 receptors, opioid receptors, acetylcholine receptors, and adrenergic systems—core pharmacology for final-year medical students preparing for clinical practice.
Afferent Nervous System Targets
These targets modulate sensory signals, particularly pain, at both the peripheral and central levels.
1. Peripheral Nervous System
TRPV1 (Vanilloid) Receptors
- Targeted by: Capsaicin
- Mechanism:
- Activates TRPV1 receptors on C-fibres → Substance P release
- Depletes Substance P at terminals → temporary analgesia until resynthesised
- Clinical Use: Topical arthritis creams
Prostaglandin (Prostanoid) Receptors
NSAIDs (e.g. Aspirin, Ibuprofen)
- Mechanism:
- Inhibit cyclooxygenase (COX) enzymes → ↓ prostaglandin synthesis
- Reduces hypersensitisation of nociceptors
- Effect: Anti-inflammatory analgesia
COX-2 Inhibitors (e.g. Celecoxib)
- Mechanism: Selectively inhibit COX-2 → fewer side effects
- Effect: Analgesic and anti-inflammatory
Peripheral Opioid Receptors
- Drugs: Codeine, Morphine, Fentanyl
- Mechanism:
- Opens K⁺ channels → efflux → neuronal hyperpolarisation
- ↓ Peripheral nociceptive signalling
2. Central Nervous System
Opioid Receptors (Central)
- Sites: Spinal cord (dorsal horn), periaqueductal grey (PAG)
- Mechanism:
- Spinal Cord: Inhibit Ca²⁺ influx at presynaptic terminals → ↓ neurotransmitter release
- PAG → NRM → Dorsal Horn: Activates descending inhibitory pain pathway
- Drugs: Morphine, Codeine, Fentanyl
Descending Inhibitory Neurons
- Drugs: Low-dose Tricyclic Antidepressants
- Mechanism:
- Inhibit reuptake of serotonin, norepinephrine, and enkephalins in dorsal horn
- Enhances endogenous inhibition of pain
Brain-Level Target
- General Anaesthetics: Induce unconsciousness via global CNS depression
Efferent Nervous System Targets
Targets in this pathway influence motor output, including voluntary and autonomic actions.
Nicotinic Acetylcholine Receptors (nAChRs)
Agonists
- Examples: Nicotine, Carbachol
- Effects: Mimic ACh → pupil constriction (e.g. glaucoma treatment)
Antagonists
- Examples: Suxamethonium, Varenicline (Champix)
- Effects: Muscle relaxation, smoking cessation
Neuromuscular Blockers
Non-Depolarising
- Mechanism: Competitive antagonists of nAChRs → inhibit ACh binding
- Reversal: Acetylcholinesterase inhibitors
- Side Effects: Hypotension, bradycardia
Depolarising
- Mechanism: Agonists → persistent depolarisation → flaccid paralysis
- Side Effects: Bradycardia, hyperkalaemia, increased intraocular pressure
- Special Risks:
- Prolonged paralysis: if AChE is absent/mutated
- Malignant hyperthermia: if SR-Ca²⁺ channel is mutated
Acetylcholinesterase (AChE)
AChE Inhibitors
- Examples: Physostigmine, Organophosphates, Tacrine
- Mechanism: Inhibit ACh breakdown → ↑ synaptic ACh
- Uses: Myasthenia gravis, Alzheimer’s, nerve gas agents
- Caution: Parasympathomimetic side effects
Other Targets
Choline Reuptake Inhibitors
- Mechanism: Block reuptake → ↑ ACh in synapse
Vesicle Exocytosis
- Drug: Botulinum toxin
- Mechanism: Blocks ACh vesicle fusion → muscle paralysis
Autonomic Nervous System Targets
Sympathetic Nervous System
Sympathomimetics (Adrenergic Agonists)
| Class | Effects & Uses |
|---|---|
| α-Agonists | Vasoconstriction (hypotension, nasal decongestants), pupil dilation |
| β-Agonists | Bronchodilation (asthma), stop premature labour, ↑HR, ↑contractility |
| Adrenaline | Mixed α/β; anaphylaxis, cardiac arrest, vasodilation, bronchodilation |
| Noradrenaline | More α-potent; vasopressor in shock |
Sympatholytics (Adrenergic Antagonists)
| Class | Effects & Uses |
|---|---|
| α-Antagonists | ↓ BP (anti-hypertensive), prostatic hypertrophy; caution: postural hypotension |
| β-Antagonists | Angina, heart failure, glaucoma; avoid in asthma due to bronchoconstriction |
Parasympathetic Nervous System
Parasympathomimetics (Muscarinic Agonists)
- Effects:
- Bradycardia, hypotension
- ↑ GI motility, secretions
- Bronchoconstriction
- Pupil constriction (↓ intraocular pressure)
- Includes: Muscarinic agonists and AChE inhibitors
Parasympatholytics (Muscarinic Antagonists)
| Drug | Target & Indication |
|---|---|
| Atropine | Non-selective; ↓ secretions, ↑ HR, antidote for AChE poisoning |
| Ipratropium | Lungs; asthma and COPD |
| Tolterodine | Bladder; urinary incontinence |
| Pirenzepine | Stomach; peptic ulcers |
Muscarinic Toxins
| Toxin | Mechanism | Effects |
|---|---|---|
| Mamba toxin | M1 antagonist | Sympathomimetic signs |
| Botulinum toxin | Inhibits ACh exocytosis | Muscle paralysis, parasympathetic failure |
| α-Bungarotoxin | Blocks post-synaptic AChRs | Neuromuscular block |
| Parathion | Irreversible AChE inhibitor | Bradycardia, hypotension (ACh excess) |
| Curare | Non-depolarising neuromuscular block | Flaccid paralysis |
Summary – Nervous System Drug Targets
Nervous system drug targets include afferent and efferent neural pathways, as well as autonomic control. Pharmacological agents act on receptors like TRPV1, opioid, nicotinic, muscarinic, and adrenergic types to modify pain, motor function, and autonomic activity. These drug targets are essential for managing pain, anaesthesia, hypertension, asthma, and neurological diseases. For a broader context, see our Pharmacology & Toxicology Overview page.