Pharmacology · ANS Introduction

ANS Organization and Functional Anatomy

The two-neuron arc, three divisions, tonic tone, and anatomical drug targets at a glance

Both the sympathetic and parasympathetic divisions use a two-neuron efferent arc: the preganglionic neuron releases ACh onto nicotinic N-N receptors in the peripheral ganglion, and the postganglionic neuron then releases norepinephrine (sympathetic) or ACh onto muscarinic receptors (parasympathetic) at the target organ.
The sympathetic division originates from T1–L2 (thoracolumbar), synapses in paravertebral chain ganglia near the spine, and projects long postganglionic fibers to targets; the adrenal medulla is a modified sympathetic ganglion that releases epinephrine and norepinephrine directly into the bloodstream.
The parasympathetic division originates from cranial nerves III, VII, IX, X and S2–S4 (craniosacral) and synapses in terminal ganglia at or within the target organ — giving long preganglionic and short postganglionic fibers; the vagus nerve supplies the heart, lungs, and most abdominal viscera.
Tonic resting tone determines the direction of a drug's effect: the heart and bronchi are under dominant parasympathetic tone (atropine → tachycardia and bronchodilation), while blood vessels are under dominant sympathetic tone (alpha-1 blockade → vasodilation and orthostatic hypotension).
Drugs can target three anatomical levels: ganglionic blockers (trimethaphan, blocking N-N receptors) disrupt both divisions simultaneously; muscarinic drugs act at parasympathetic neuroeffector junctions; adrenergic drugs act at sympathetic neuroeffector junctions with selectivity determined by receptor subtype.

Abbreviations: ANS = autonomic nervous system · ACh = acetylcholine · NE = norepinephrine · CNS = central nervous system · N-N = nicotinic neuronal receptor · ENS = enteric nervous system

The Two-Neuron Efferent Arc

Both sympathetic and parasympathetic divisions

Central Nervous System Preganglionic Neuron

→ ACh → Nicotinic N-N

Peripheral Ganglion Postganglionic Neuron

→ Symp: NE • Para: ACh

Target Organ Effector Cell

The ganglionic synapse uses ACh on nicotinic N-N receptors in both divisions. Ganglionic blockers (trimethaphan) disrupt both simultaneously — producing orthostatic hypotension, ileus, urinary retention, and anhidrosis.

Three Divisions

Division 1

Sympathetic

OriginT1–L2 (thoracolumbar)

GangliaNear spine (paravertebral chain)

Pre/PostShort pre / long post

Post TXNorepinephrine

AdrenalModified ganglion; releases epinephrine + NE into blood

Division 2

Parasympathetic

OriginCN III, VII, IX, X; S2–S4 (craniosacral)

GangliaTerminal (at or within target organ)

Pre/PostLong pre / short post

Post TXAcetylcholine (muscarinic)

VagusHeart, lungs, most abdominal viscera

Division 3

Enteric

LocationGut wall (esophagus to anus)

PlexusesMyenteric (motility) + Submucosal (secretion)

Key TXSerotonin, ACh, nitric oxide

AutonomyFunctions without extrinsic input

Drug noteOpioids suppress motility via mu receptors

Dominant Resting Tone by Organ

Organ	Dominant Resting Tone	Drug Consequence
Heart (sinoatrial node)	Parasympathetic	Atropine → tachycardia; vagotomy → rate rises to intrinsic ~100 bpm
Blood vessels	Sympathetic	Alpha-1 blocker (prazosin) → vasodilation, orthostatic hypotension
Pupil	Parasympathetic	Atropine → mydriasis; muscarinic agonist → miosis
Bronchi	Parasympathetic	Ipratropium (muscarinic blocker) → bronchodilation in COPD
Gastrointestinal motility	Parasympathetic	Opioids suppress ENS → constipation

Anatomical Drug Target Levels

Target Level 1

Ganglionic Blockers

Block nicotinic N-N receptors at autonomic ganglia. Disrupt both sympathetic and parasympathetic divisions simultaneously. Example: trimethaphan. Indiscriminate profile — orthostatic hypotension, ileus, urinary retention.

Target Level 2

Muscarinic Drugs

Act at parasympathetic neuroeffector junctions. Agonists (pilocarpine) mimic parasympathetic activation. Antagonists (atropine) block it. Organ specificity from muscarinic receptor subtype distribution.

Target Level 3

Adrenergic Drugs

Act at sympathetic neuroeffector junctions and on adrenal-medullary catecholamine targets. Selectivity determined by receptor subtype: alpha-1, alpha-2, beta-1, beta-2.

Suggested References

Author / Organization	Title	Source
Katzung BG (ed)	Basic and Clinical Pharmacology, 15th ed. Chapters 6–9: Autonomic Nervous System Pharmacology	McGraw-Hill, 2021
Brunton LL, Knollmann BC (eds)	Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed. Chapter 8: Neurotransmission: The Autonomic and Somatic Motor Nervous Systems	McGraw-Hill, 2023
Janig W, McLachlan EM	Characteristics of function-specific pathways in the sympathetic nervous system	Trends Neurosci. 1992;15(12):475–481
Jansen ASP, Van Nguyen X, Karpitskiy V, et al	Central command neurons of the sympathetic nervous system: basis of the fight-or-flight response	Science. 1995;270(5236):644–646
Goldstein DS, Eisenhofer G, Kopin IJ	Sources and significance of plasma levels of catechols and their metabolites in humans	J Pharmacol Exp Ther. 2003;305(3):800–811
Wehrwein EA, Orer HS, Barman SM	Overview of the anatomy, physiology, and pharmacology of the autonomic nervous system	Compr Physiol. 2016;6(3):1239–1278
Breit S, Kupferberg A, Rogler G, Hasler G	Vagus nerve as modulator of the brain-gut axis in psychiatric and inflammatory disorders	Front Psychiatry. 2018;9:44
Furness JB	The enteric nervous system and neurogastroenterology	Nat Rev Gastroenterol Hepatol. 2012;9(5):286–294
Bornstein JC, Costa M, Grider JR	Enteric motor and interneuronal circuits controlling motility	Neurogastroenterol Motil. 2004;16(Suppl 1):34–38
Saper CB	The central autonomic nervous system: conscious visceral perception and autonomic pattern generation	Annu Rev Neurosci. 2002;25:433–469
Michel MC, Vrydag W	Alpha1-, alpha2- and beta-adrenoceptors in the urinary bladder, urethra and prostate	Br J Pharmacol. 2006;147(Suppl 2):S88–S119
Cazzola M, Page CP, Calzetta L, Matera MG	Pharmacology and therapeutics of bronchodilators	Pharmacol Rev. 2012;64(3):450–504