Neurotransmitters

ACh is the main player.

• Somatic (Motor): ACh (single neuron)
• Parasympathetic: ACh → ACh
• Sympathetic (Standard): ACh → NE
  • Sympathetic (Sweat Glands): ACh → ACh
  • Sympathetic (Adrenal Medulla): ACh → Epi/NE (blood)

System	Preganglionic Neuron Neurotransmitter	Postganglionic Neuron Neurotransmitter / Adrenal Medulla Release	Target Organ(s) / Systemic Effect
Motor (Somatic)	ACh (Single motor neuron)	N/A (No postganglionic neuron)	Skeletal Muscle
Sympathetic	ACh	1. Typical Targets: NE (α/β adrenergic receptors) 2. Eccrine (Thermo): ACh (M receptors) 3. Apocrine/Stress Eccrine: NE (α1 adrenergic receptors). Also sensitive to circulating Epi/NE. 4. Adrenal Medulla: Hormones (primarily Epi, some NE) into bloodstream	1. Smooth/Cardiac muscle, Glands; Contraction/Relaxation, ↑HR/Force, Secretion 2. ↑Thermo Sweating 3. ↑Stress Sweating 4. Systemic “Fight/Flight” effects
Parasympathetic	ACh	ACh (M receptors).	Smooth/Cardiac muscle (↓HR), Glands (“Rest & Digest” functions)

Neurotransmitter & Receptor Pair	Functions in the CNS
Ionotropic: Ligand-gated ion channels	Transmembrane proteins that allow ions to cross the membrane
Glutamate [E] → NMDA receptor: Ca2+ & Na+ influx	Long-term potentiation of learning & memory
GABA [I] → GABAA receptor: Cl− & HCO3− influx	Sedation, anxiolytic & anticonvulsive
Glycine [I] → Glycine receptor: Cl− influx	Inhibit spinal interneurons (prevents spasticity)
Metabotropic: G protein-coupled receptors	Act through second messengers (eg, cAMP, PKA)
Dopamine → D1-5 receptors	Modulate attention, movement & reward
Serotonin → 5-HT receptors	Modulate mood, nausea & trigeminovascular nociception (migraine)
Norepinephrine → α & β adrenoceptors	Promotes vigilance, attention & emotional memory
Histamine → H3 receptors	Promotes wakefulness

• Acetylcholine
  • Usually excitatory
  • Increased levels
    • Parkinson disease
  • Decreased levels
    • Alzheimer disease, Acetylcholine and Alzheimer’s both start with A
    • Huntington disease
• Dopamine
  • Drive to GET a reward. NOT the feeling of reward. Both excitatory and inhibitory
    • D1 receptor: Subsequent activation of protein kinase A causes smooth muscle relaxation
    • D2 receptor: located mainly in the substantia nigra, striatum, area postrema, and pituitary gland.
    • See dopaminergic pathway
  • Increased levels
    • Schizophrenia
    • Huntington disease
  • Decreased levels
    • Depression
    • Parkinson disease
    • Neuroleptic malignant syndrome (D2 receptor blocked)

Functions of dopamine

D rugs psych O sis P rolactin inhibition A ttention M otivation I nvoluntary movements N ausea E nergy

• Norepinephrine
  • Alertness
  • Increased levels
    • Anxiety
  • Decreased levels
    • Depression
• Serotonin (aka 5-HT)
  • Satiety, Tranquilty, Peace
  • Increased levels
    • Serotonin syndrome
  • Decreased levels
    • Anxiety
    • Depression
    • Parkinson disease
• GABA
  • GABA A receptor mediates a fast response to GABA because it is an ion-gated chloride channel. Activation of this receptor leads to rapid muscle relaxation and sedation. Its activity is enhanced by benzodiazepines, which can be used to treat spasticity.
  • GABA B receptor mediates a slower response to GABA because it is mediated by a G protein–coupled receptor that opens potassium channels. It is agonized by baclofen, which can also be used to treat spasticity.
  • Inhibitory in the brain
  • Increased levels
  • Decreased levels
    • Anxiety
    • Huntington disease
• Histamine
  • Wakefulness. Think about benadryl (antihistamine) makes us drowsy and sleepy)
• Glutamate
  • The primary excitatory neurotransmitter in the CNS.
  • Receptors: NMDA, AMPA, Kainate.
  • Clinical Correlation: Excitotoxicity (e.g., in stroke) is mediated by excessive glutamate release, leading to ↑ intracellular Ca²⁺ and subsequent neuronal death.
  • GlutaMATE
• GABA (γ-aminobutyric acid)
  • The primary inhibitory neurotransmitter in the CNS (brain).
  • Synthesized from glutamate by glutamate decarboxylase (requires Vitamin B6).
  • Receptors:
    • GABA-A: Ligand-gated Cl⁻ channel. Target for Benzodiazepines, Barbiturates, and alcohol.
    • GABA-B: G-protein coupled receptor.
• Glycine
  • The primary inhibitory neurotransmitter in the spinal cord.
  • Receptors: Ligand-gated Cl⁻ channel.
  • Clinical Correlation: Strychnine is an antagonist, causing massive tetanic contractions.

Feature	GABA	Glycine
Primary Location	Brain	Spinal Cord & Brainstem
Precursor	Glutamate	Serine
Receptor Blocked by	Bicuculline	Strychnine
Dual Role	No (purely inhibitory)	Yes (inhibitory + co-agonist at NMDA receptors)
Disease Example	Seizures, Anxiety (low GABA)	Tetanus, Strychnine poisoning (blocked glycine action)