This is a mechanism module, not a specific disease. Do NOT create a "D2 Receptor Antagonism" Disease entry. Disorder entries reference individual nodes via conforms_to, for example "d2_receptor_antagonism#D2/3 Receptor Antagonist Occupancy".
The drug acts downstream of the lesion, and that is worth stating because it is unusual among these modules. The cited imaging review places striatal D2/3 blockade "downstream of the likely principal dopaminergic pathophysiology in schizophrenia", which is presynaptic. So a conforming psychosis entry keeps its own dopamine-dysregulation node as the disease mechanism and conforms here for the drug's site of action; the two are not the same claim, and the module does not assert that D2 blockade corrects the presynaptic abnormality.
Three things the module declines to model. First, a mesolimbic-versus-nigrostriatal split between the therapeutic and motor arms: it is the standard account, but no sentence in the cited sources supports it, which is why both arms hang off striatal occupancy and are separated by degree rather than by territory. A curator who finds a citable source should add the territories. Second, tardive dyskinesia, which is a distinct late syndrome whose mechanism the literature does not settle - the one review read for this module calls the dopamine-hypersensitivity account no longer viable - so it would be a new module rather than another arm here. Third, the non-D2 pharmacology every atypical antipsychotic also carries (5-HT2A, H1, muscarinic, alpha-1): a conforming entry should conform here for the D2 half and describe the rest separately, as the AT1 module asks of sparsentan.
The antiemetic arm is the one with the thinnest evidence. The source establishes that D2 receptors are implicated in the vomiting act; the step from that to an antagonist suppressing emesis is an inference, and the node's evidence is graded accordingly. The obvious conformer is Chemotherapy_Induced_Nausea_and_Vomiting, but it carries no D2-antagonist treatment today, so wiring it would mean adding a treatment rather than wiring an existing one.
D2/3 Receptor Antagonist Occupancy
trigger
An antipsychotic or a D2-antagonist antiemetic occupies striatal D2 and D3 receptors. This is the one action every licensed drug in the class shares, and it is where conformance belongs: the agents differ widely in everything else they bind, and in how much of the receptor they occupy at a clinical dose.
Downstream
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Loss of D2-Mediated Gi/Go Inhibition of Adenylyl Cyclase
Occupancy removes the signal the receptor would otherwise transduce.
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Loss of Lactotroph D2 Restraint of Prolactin Secretion
The same drug reaches D2 receptors on anterior pituitary lactotrophs. Attached here rather than below the striatal arms because the pituitary sits outside the blood-brain barrier and is reached at concentrations the striatal occupancy figure does not predict.
Show evidence (1 reference)
"These studies show that all currently licensed antipsychotic drugs block striatal D2/3 receptors in vivo- a site downstream of the likely principal dopaminergic pathophysiology in schizophrenia"
Sources both halves of this node - that the whole class shares this receptor action, and that the action sits downstream of the presynaptic abnormality a conforming psychosis entry models separately.
Antipsychotic Response Above an Occupancy Threshold
consequence
The therapeutic consequence, and the reason the module is organised by degree of occupancy: response requires occupancy above a threshold, and the source is explicit that blockade is necessary without being sufficient. The node therefore claims a dose-dependent antipsychotic effect, not that D2 blockade explains recovery.
Show evidence (1 reference)
"Adequate D2/3 blockade by antipsychotic drugs is necessary but not always sufficient for antipsychotic response."
Sources this node's claim and its limit in one sentence. Quoted deliberately in preference to the bare threshold statement, because it is the half a reader is likely to forget.
Loss of Lactotroph D2 Restraint of Prolactin Secretion
adverse effect
Prolactin release from anterior pituitary lactotrophs is held down by dopamine acting at D2, so blockade raises it. The arm hangs off receptor occupancy rather than below the striatal steps for a reason the cited study makes precisely: the anterior pituitary is outside the blood-brain barrier, and for the antipsychotics that P-glycoprotein pumps out of the brain the drug concentration there is higher than in brain, so prolactin rises more than the striatal occupancy figure would predict. That is also why the module does not treat prolactin as simply another point on the occupancy curve.
Show evidence (2 references)
"Risperidone, paliperidone, and amisulpride are associated with higher prolactin levels than would be anticipated from striatal dopamine receptor occupancy studies."
Sources the claim that this arm is not predicted by striatal occupancy, which is why it is modelled separately rather than as another threshold on the same curve.
"P-gp has high affinity to all these antipsychotics and selectively removes them from the brain and concentrates them in the blood draining the hypothalamus, allowing greater dopamine receptor blockade in the cells in the anterior pituitary that produce prolactin."
Sources the mechanism behind the dissociation - the pituitary's position outside the barrier plus efflux from brain - and the cell type this node binds.
Suppression of Emesis
consequence
The second therapeutic indication of the class, and the reason a D2 antagonist appears in entries that have nothing to do with psychosis. The evidence here is the module's weakest: the cited review establishes that D2 receptors participate in the vomiting act, and the step from that to an antagonist suppressing emesis is an inference this node makes explicit rather than hiding. No node is bound to a vomiting-centre anatomical site, because the source quoted here names the receptor among several without localising the D2 component.
Show evidence (1 reference)
"Likewise, Dopamine type 2 (D2) receptors, dopamine neurotransmitter, Muscarinic receptors (M3), GLP1 receptors, and histaminergic receptors (H1) are also implicated in the vomiting act as well."
Establishes that D2 receptors participate in emesis, which is what blockade acts on. Graded INDIRECT because the source describes the receptor's role in vomiting rather than an antagonist's effect on it.
Antipsychotic Therapy
Platform:
Small molecule
The typical and atypical antipsychotics, whose shared action is the D2/3 occupancy this module's trigger records. Listed as one treatment because that action is what they have in common; their other receptor pharmacology differs and is out of scope here.
D2-Antagonist Antiemetic Therapy
Platform:
Small molecule
Metoclopramide and the phenothiazine antiemetics, given for nausea and vomiting rather than for psychosis, and reaching the same receptor. Metoclopramide's prokinetic action on gut motility is a second effect this module does not carry.