| Criteria | Ionotropic Glutamate Receptor (iGluR) | Metabotropic Glutamate Receptor (mGluR) | Remarks |
| Receptor Type | Ligand-gated ion channel | G-protein-coupled receptor (GPCR) | iGluRs are fast-acting ion channels; mGluRs are slower, G-protein-mediated modulators |
| Activation Mechanism | Glutamate binding directly opens an ion channel, allowing ion flow | Glutamate binding activates intracellular G-proteins, leading to second messenger cascades | Direct (iGluR) vs. indirect (mGluR) activation |
| Response Speed | Very fast (milliseconds) | Slower (hundreds of milliseconds to seconds) | iGluRs mediate rapid synaptic transmission; mGluRs modulate long-term signaling |
| Ion Permeability | Na⁺, K⁺, and sometimes Ca²⁺ (depending on subtype) | No direct ion conductance | Only iGluRs function as ion channels |
| Subtypes | AMPA, NMDA, and Kainate receptors | Group I, II, and III mGluRs (mGluR1–mGluR8) | iGluRs are classified by pharmacology; mGluRs are grouped by signaling properties |
| Primary Function | Mediate fast excitatory synaptic transmission | Modulate synaptic strength, neuronal excitability, and plasticity | iGluRs = fast excitatory drive; mGluRs = modulatory control |
| Location in Neurons | Postsynaptic membranes (mostly dendritic spines) | Both pre- and postsynaptic membranes | mGluRs can regulate neurotransmitter release presynaptically |
| Second Messengers | None (direct ion flow) | Activates second messengers like cAMP, IP₃, DAG | mGluRs can influence multiple intracellular signaling pathways |
| Role in Plasticity | Directly contribute to LTP and LTD via calcium influx (especially NMDA subtype) | Indirectly modulate LTP and LTD through kinase/phosphatase pathways | Both affect synaptic plasticity but via different mechanisms |
| Pharmacological Targeting | Targeted by antagonists/agonists for epilepsy, neurodegeneration, and psychiatric disorders | Targeted for chronic pain, anxiety, depression, and neurodegeneration | Both receptor types are important drug targets, but with distinct therapeutic applications |
