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GPCRs (G-protein coupled receptors) matter because they explain why many psychiatric drugs act slowly and produce widespread, modulatory effects rather than an instant on-off switch. A GPCR is a metabotropic receptor (one that works indirectly through a chemical cascade), unlike an ionotropic receptor, which directly opens an ion channel. For example, imagine two receptors both activated by the same neurotransmitterA chemical messenger that nerve cells release to signal to the next cell.Read more →: one opens instantly and the signal ends within milliseconds, while the other triggers a slower chain reaction lasting seconds and adjusting how the whole cell behaves. In practice, most monoamine receptors, including serotonin, noradrenaline, and dopamine receptor subtypes, and receptors such as muscarinic acetylcholine and GABAThe brain's main calming (inhibitory) chemical messenger, boosted by benzodiazepines and alcohol.Read more →-B, work this slower, GPCR way.

When a neurotransmitterA chemical messenger that nerve cells release to signal to the next cell.Read more → binds a GPCR, it activates an attached G-protein, which then activates an effector enzyme inside the cell, rather than opening an ion channel directly. One major pathway uses adenylyl cyclase (an enzyme) to produce cAMP (cyclic adenosine monophosphate), a second messenger, a chemical relay signal inside the cell, that goes on to alter many downstream proteins. A second major pathway uses phospholipase C (a different enzyme) to produce two second messengers at once, IP3 (inositol trisphosphate) and DAG (diacylglycerol), which release calcium and activate other enzymes respectively. Say a muscarinic acetylcholine receptor, a GPCR, activates phospholipase C: this produces IP3 and DAG together, triggering a broader, slower cellular response than a single ion channel opening ever could. In practice, this multi-step cascade amplifies the original signal, since one receptor can activate many G-proteins, which is why GPCR signalling can be slower to start but longer-lasting and more widespread than ionotropic signalling.

• Which second messenger pathway does the inositol depletion hypothesis of lithium concern?
• What happens to cyclic AMP when a Gi-coupled receptor such as the dopamine D2 receptorThe main dopamine receptor subtype that antipsychotic drugs block to reduce psychotic symptoms.Read more → is activated?
• Which receptor change is proposed to explain why antidepressants take weeks to work?

• GPCR (G-protein coupled receptor), a metabotropic receptor acting via a G-protein and second messenger, unlike an ionotropic receptor which directly opens an ion channel.
• cAMP pathway, produced by adenylyl cyclase downstream of certain GPCRs, whereas the IP3/DAG pathway is produced by phospholipase C downstream of others.
• GABA-B receptor, a slow, modulatory GPCR, unlike the GABA-A receptorA receptor for the calming brain chemical GABA, and the site where benzodiazepines and alcohol produce their sedating effect.Read more → which is a fast ionotropic chloride channel.
• Ionotropic receptor signalling, occurs within milliseconds via direct channel opening, rather than the seconds-long cascade typical of GPCR signalling.

• GABAThe brain's main calming (inhibitory) chemical messenger, boosted by benzodiazepines and alcohol.Read more →-A is an ionotropic receptor rather than a second messenger pathway.
• Stimulation of adenylate cyclase follows Gs rather than Gi coupling.
• Lithium also affects adenylate cyclase, but the depletion hypothesis concerns inositol.
• Sodium channel blockade describes lamotrigine and carbamazepine.
• Alpha-2-delta binding describes gabapentin and pregabalin.

• Localise the clue to the relevant anatomical level, cell type, pathway or molecular process.
• Map that structure or process to its normal function.
• Predict the deficit or clinical sign produced when it is disrupted.
• Reject options that belong to a neighbouring structure, pathway or level of explanation.