Neurotransmitters

A neurotransmitter is a chemical messenger released by a neuron into the synaptic cleft — the gap between two neurons — that alters the activity of the receiving (postsynaptic) neuron by binding to specialised receptor proteins. To qualify as a neurotransmitter by classical criteria, a substance must be synthesised in the neuron, released in response to neuronal activity, produce a defined effect on the postsynaptic cell, and be removed from the synapse by a specific mechanism. The major neurotransmitters include glutamate (the brain's primary excitatory transmitter), GABA (the primary inhibitory transmitter), acetylcholine, and the monoamines — dopamine, serotonin, and norepinephrine.

Ionotropic receptors are ion channels that open directly when a neurotransmitter binds to them, allowing specific ions to flow across the membrane within milliseconds — producing fast, localised changes in excitability. Examples include AMPA, NMDA, and GABA-A receptors. Metabotropic receptors are G-protein-coupled receptors that do not control ion channels directly; instead they trigger intracellular signalling cascades that produce slower, longer-lasting changes in neuronal activity over seconds to minutes. Dopamine, serotonin, and muscarinic acetylcholine receptors are metabotropic. The clinical implication is that drugs targeting metabotropic receptors tend to have more prolonged effects and more diffuse targets than those acting on ionotropic channels.

Most psychiatric drugs act by manipulating one of three points in the neurotransmitter cycle: synthesis, release, or termination. Reuptake inhibitors (SSRIs, SNRIs, amphetamines) block transporter proteins to increase the concentration of transmitter in the synapse. Receptor agonists mimic a transmitter and activate its receptors; antagonists block receptors and reduce signalling. Enzyme inhibitors (e.g., MAO inhibitors) slow the degradation of monoamines, increasing their availability. Some drugs act on autoreceptors — presynaptic receptors through which the neuron monitors its own transmitter release and adjusts output accordingly. The specificity and therapeutic window of a drug depends on which receptor subtypes it targets and in which brain regions they are expressed.

The terms describe different modes of action rather than different molecules — the same substance can act as both depending on context. Classical neurotransmitters act rapidly at discrete, well-defined synapses, directly changing the firing probability of a specific postsynaptic neuron. Neuromodulators — typically the monoamines and acetylcholine — act more diffusely, released from widespread projection systems to modulate the gain or sensitivity of large neuronal populations without directly driving or suppressing firing. In practice, dopamine, serotonin, and norepinephrine are often described as neuromodulators because their primary function is to bias information processing broadly (setting the 'tone' for reward, mood, and arousal) rather than to carry specific sensory or motor signals.