Discuss the major neurotransmitters, their receptors, functions, and clinical significance.

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: February 15, 2026 • View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Major Neurotransmitters: Functions, Receptors, and Clinical Significance

Overview of Neurotransmitter Classification

Neurotransmitters are chemical messengers that transmit signals across synapses, essential for all nervous system functions including cognition, movement, emotion, and pain processing. 1, 2

Excitatory Neurotransmitters

Glutamate

Glutamate is the primary excitatory neurotransmitter in the central nervous system, critical for learning, memory formation, and synaptic plasticity. 1

  • Receptor types: Acts primarily through ionotropic receptors including NMDA receptors, which mediate fast synaptic transmission and are essential for excitatory postsynaptic potentials 1
  • Additional receptors: Metabotropic glutamate receptor type 5 (mGluR5) provides modulatory functions 3
  • Clinical significance in chronic pain: Enhanced glutamate release at the spinal dorsal horn contributes to central sensitization and chronic pain states, where continuous nociceptive input reaches the brain even after initial noxious stimulation ceases 3
  • Pathological states: Dysregulation leads to excitotoxicity in neurodegenerative conditions; increased NMDA receptor binding is observed in focal epilepsy 3

Inhibitory Neurotransmitters

GABA (Gamma-Aminobutyric Acid)

GABA is the major inhibitory neurotransmitter in the brain, counterbalancing glutamate's excitatory effects. 4

  • Function: Essential for maintaining the excitatory-inhibitory balance necessary for normal brain function 4
  • Clinical significance in pain: Loss of GABAergic interneurons in the spinal cord contributes to chronic pain development by reducing inhibitory control 3
  • Therapeutic applications: GABAergic drugs are used for anxiety and epilepsy treatment 1

Monoamine Neurotransmitters

Serotonin (5-HT)

Serotonin is critical for mood regulation, sleep cycles, and descending pain inhibitory pathways. 1

  • Receptor subtypes: 5-HT1A receptors are extensively studied; reduced binding in the ipsilateral temporal lobe helps identify epileptogenic zones in temporal lobe epilepsy 3
  • Pain modulation: Plays a key role in descending pain control pathways originating from the periaqueductal grey (PAG) and rostral ventromedial medulla 3, 1
  • Clinical applications: Selective serotonin reuptake inhibitors (SSRIs) target this system for depression treatment 1
  • Pathological findings: Reduced brainstem and limbic serotonin binding may explain affective symptoms in temporal lobe epilepsy patients 3

Dopamine

Dopamine is essential for reward processing, motor control, and motivation, with dysregulation linked to Parkinson's disease and addiction. 1

  • Receptor subtypes: D1 receptors, D2/D3 receptors, and dopamine transporter systems are all therapeutic targets 3
  • Clinical imaging findings: Generally reduced dopamine uptake is observed in drug-resistant epilepsy; increased uptake in the epileptogenic region occurs in temporal lobe epilepsy 3
  • Therapeutic targets: Dopamine precursors like levodopa are used for Parkinson's disease 1

Norepinephrine (Noradrenaline)

Noradrenergic reuptake inhibition is considered the main mechanism for controlling visceral pain. 1

  • Pain control mechanism: Enhances natural pain inhibition pathways through descending modulation 1
  • Clinical applications: Serotonin-norepinephrine reuptake inhibitors (SNRIs) are effective for pain control by enhancing these pathways 1

Epinephrine (Adrenaline)

  • Function: Mediates the "fight-or-flight" response and sympathetic nervous system activation 1

Cholinergic System

Acetylcholine

Acetylcholine is the primary neurotransmitter at neuromuscular junctions and is critical for memory, learning, and autonomic functions. 1

  • Receptor types: Nicotinic acetylcholine receptors (α4β2 subtype) show regional binding increases in autosomal dominant nocturnal frontal lobe epilepsy and idiopathic generalized epilepsy 3
  • Clinical significance: Cholinergic dysfunction is implicated in Alzheimer's disease and myasthenia gravis 2

Neuropeptides and Other Signaling Molecules

Substance P

  • Function: A neuropeptide involved in pain transmission and inflammatory responses 1
  • Role in chronic pain: Released along with glutamate and CGRP at the spinal dorsal horn during prolonged noxious stimulation, contributing to sensitization of postsynaptic neurons and glial activation 3

Opioid Peptides

Three main opioid receptor types (μ, κ, and δ) modulate pain through endogenous peptides including endorphins, enkephalins, and dynorphins. 1

  • Clinical findings: Post-ictal increases in opioid receptor binding occur in the ipsilateral temporal region in temporal lobe epilepsy 3
  • Pain modulation: Higher binding in epileptogenic regions suggests compensatory pain control mechanisms 3

ATP (Adenosine Triphosphate)

  • Dual function: Serves as both an energy source and signaling molecule in nociceptive pathways 1

Nitric Oxide (NO)

  • Function: A diffusible gas neurotransmitter involved in vasodilation and nociceptive processes 1

Clinical Significance and Therapeutic Applications

Neuroimaging of Neurotransmitter Systems

Advanced PET imaging techniques can visualize neurotransmitter receptor binding in various neurological conditions, providing diagnostic and research insights. 3

  • Synaptic density markers: Synaptic vesicle glycoprotein 2A (SV2A) serves as a marker of synaptic density and is the binding site for levetiracetam; lower SV2A is detected in epileptic lesions 3
  • Neuroinflammation markers: Translocator protein (TSPO) signal increases in epileptic lesions as a proxy for neuroinflammation, associated with reduced glucose metabolism 3

Chronic Pain Pathophysiology

In chronic pain states, prolonged noxious stimulation sensitizes peripheral nerve endings, leading to enhanced neuronal firing and increased neurotransmitter release that activates microglia and astrocytes toward neuroinflammatory states. 3

  • Descending facilitation: The periaqueductal grey and rostral ventromedial medulla shift from inhibitory to facilitatory pain control, amplifying nociceptive signals 3
  • Neuronal network imbalance: Loss of inhibitory interneurons combined with enhanced postsynaptic signaling perpetuates pathological pain 3
  • Hippocampal changes: Reduced neurogenesis dependent on TNF-α signaling is associated with both chronic pain and depression, explaining comorbidity 3

Pharmacological Targeting

Many medications target specific neurotransmitter systems to treat neurological and psychiatric disorders. 1

  • Depression: SSRIs and SNRIs enhance serotonin and norepinephrine signaling 1
  • Parkinson's disease: Dopamine precursors restore dopaminergic function 1
  • Epilepsy and anxiety: GABAergic drugs enhance inhibitory neurotransmission 1
  • Pain syndromes: SNRIs provide analgesia through enhanced descending inhibition 1

Common Pitfalls and Clinical Considerations

  • Medication interactions: Antiseizure medications significantly influence neurotransmitter receptor binding and plasma free fractions of imaging tracers, which can confound diagnostic imaging 3
  • Compensatory mechanisms: Contralateral increases in receptor binding may represent compensatory responses rather than primary pathology 3
  • Comorbidity recognition: Shared neurotransmitter dysfunction in the hippocampus links chronic pain with major depressive disorder, requiring integrated treatment approaches 3
  • Glial activation: Chronic pain involves not just neuronal changes but also microglial and astrocyte activation, requiring anti-inflammatory strategies beyond traditional analgesics 3

References

1
Guideline

Neurotransmitter Functions and Clinical Significance

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

3
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Related Questions

What are neurotransmitters and their role in brain function?
What are the different types of neurotransmitters?
How are neurotransmitters that modulate multiple neuropsychological processes treated?
What is nerve cell physiology?
What is the primary neurotransmitter?
How should Lulican Forte (ciclopirox) lotion be applied to treat toenail onychomycosis?
How should I evaluate and manage anterior lower leg pain, including assessment for compartment syndrome, deep‑vein thrombosis, stress fracture, and shin‑splints?
For a child with mild to moderate dehydration due to diarrhea, should I use Pedialyte (oral rehydration solution) instead of a hydration multiplier (athlete electrolyte drink), and what dosing is recommended?
Is it safe to prescribe baclofen together with trazodone for a patient with spasticity and depression/insomnia, and what precautions are needed, especially in older adults or those with hepatic or renal impairment?
What are the current Global Initiative for Asthma (GINA) guidelines for stepwise asthma management, including preferred reliever therapy with inhaled corticosteroid (ICS) plus short‑acting β2‑agonist (SABA) and maintenance options such as inhaled corticosteroid (ICS)‑long‑acting β2‑agonist (LABA) regimens?
I have had a cough and wheeze for one week without a prior diagnosis; what evaluation and management are recommended?

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.

Ask Question