Neurotransmitters and Receptors

Glutamate

Primary excitatory neurotransmitter in CNS; involved in learning, memory, synaptic plasticity, and excitotoxicity

Ionotropic glutamate receptors

Include AMPA, NMDA, and Kainate receptors; fast synaptic transmission

AMPA receptor

Ionotropic glutamate receptor that conducts Na⁺ ions; mediates fast EPSPs

NMDA receptor

Ionotropic glutamate receptor requiring glutamate + glycine and membrane depolarization to remove Mg²⁺ block; conducts Ca²⁺; essential for long-term potentiation

NMDA receptor antagonists

Include ketamine and memantine; used in anesthesia and Alzheimer’s respectively

Excitotoxicity

Neuronal injury caused by excess glutamate-induced Ca²⁺ influx via NMDA receptors

GABA

Primary inhibitory neurotransmitter in brain; synthesized from glutamate by GAD

GABA_A receptor

Ionotropic Cl⁻ channel; causes fast hyperpolarization (IPSP)

GABA_A modulators

Benzodiazepines, barbiturates, and ethanol enhance GABA_A receptor activity

GABA_B receptor

Metabotropic receptor (Gi-coupled); increases K⁺ efflux or decreases Ca²⁺ influx; slower inhibition

Baclofen

GABA_B agonist used as a muscle relaxant in spasticity

Acetylcholine (ACh)

Synthesized from choline and acetyl-CoA by choline acetyltransferase (ChAT); degraded by acetylcholinesterase

Nicotinic receptor

Ionotropic ACh receptor; found at NMJs and autonomic ganglia

Nicotinic N_M receptor

Located on skeletal muscle; causes depolarization and contraction

Nicotinic N_N receptor

Found in autonomic ganglia and CNS; mediates fast synaptic transmission

Muscarinic receptor

Metabotropic ACh receptors; M1, M3, M5 (Gq); M2, M4 (Gi)

M1 receptor

Gq-coupled; activates IP₃/DAG/Ca²⁺ signaling; involved in cognition and gastric acid secretion

M2 receptor

Gi-coupled; decreases cAMP; slows heart rate via vagal stimulation

Curare

Blocks nicotinic receptors at NMJ → flaccid paralysis

Botulinum toxin

Inhibits SNARE-mediated ACh vesicle fusion → muscle paralysis

Myasthenia gravis

Autoimmune disease against nicotinic ACh receptors at NMJ; leads to muscle weakness

Dopamine

Catecholamine neurotransmitter; involved in reward, mood, and movement

Dopamine synthesis

Tyrosine → L-DOPA → dopamine (via tyrosine hydroxylase and DOPA decarboxylase)

D1-like receptors (D1, D5)

Gs-coupled; increase cAMP; excitatory

D2-like receptors (D2, D3, D4)

Gi-coupled; decrease cAMP; inhibitory

Dopamine in Parkinson’s disease

Deficiency in substantia nigra → basal ganglia dysfunction

L-DOPA therapy

Crosses BBB and is converted to dopamine; used to treat Parkinson’s

Antipsychotics

D2 receptor antagonists; treat schizophrenia by reducing dopaminergic overactivity

Norepinephrine (NE)

Released from sympathetic nerve terminals and locus coeruleus in brainstem

Alpha-1 receptor

Gq-coupled; causes vasoconstriction of blood vessels

Alpha-2 receptor

Gi-coupled; inhibits NE release via presynaptic negative feedback

Beta-1 receptor

Gs-coupled; increases HR and contractility in heart

Beta-2 receptor

Gs-coupled; causes bronchodilation and vasodilation of skeletal muscle vasculature

Beta-blockers

Propranolol, atenolol; reduce HR, treat HTN and anxiety

Serotonin (5-HT)

Synthesized from tryptophan; regulates mood, sleep, GI motility

5-HT₁A receptor

Gi-coupled; targeted by anxiolytics like buspirone

5-HT₂A receptor

Gq-coupled; targeted by psychedelics (LSD, psilocybin); involved in hallucinations

5-HT₃ receptor

Ionotropic receptor; mediates vomiting; targeted by ondansetron

SSRI drugs

Fluoxetine, sertraline; inhibit reuptake of 5-HT to treat depression

Histamine

Made from histidine; involved in wakefulness, allergy, gastric acid secretion

H1 receptor

Gq-coupled; causes vasodilation, bronchoconstriction; targeted by antihistamines

H2 receptor

Gs-coupled; stimulates gastric acid production

H3 receptor

Gi-coupled; presynaptic autoreceptor; inhibits histamine release

Opioids

Endorphins, enkephalins, dynorphins; act on μ, δ, κ GPCRs to reduce pain perception

μ-opioid receptor

Main target of morphine and heroin; causes analgesia and euphoria

Naloxone

μ-opioid receptor antagonist used to reverse opioid overdose

SNARE proteins

Mediate synaptic vesicle docking and fusion with presynaptic membrane

Synaptotagmin

Ca²⁺ sensor on synaptic vesicle that triggers fusion upon Ca²⁺ influx

Tetanus toxin

Inhibits GABA/glycine vesicle release in spinal interneurons → spastic paralysis

Glial glutamate transporters

Remove excess glutamate from synaptic cleft to prevent excitotoxicity

Reuptake transporters

Reabsorb monoamines (DA, NE, 5-HT) into presynaptic terminal (e.g., DAT, SERT)

Monoamine oxidase (MAO)

Breaks down dopamine, norepinephrine, serotonin; targeted by MAO inhibitors

COMT

Catechol-O-methyltransferase; degrades dopamine and norepinephrine extracellularly

Receptor desensitization

Prolonged stimulation of GPCRs may reduce receptor responsiveness via internalization or phosphorylation

Neuromodulation

Neurotransmitters like dopamine and serotonin modify the strength of synaptic transmission rather than directly causing depolarization/hyperpolarization

Ionotropic receptors

Ligand-gated ion channels; mediate fast synaptic transmission

Metabotropic receptors

GPCRs; slower, modulatory signaling via second messenger