History of the dopamine hypothesis of antipsychotic action

Table 1 Major steps in the dopamine hypothesis of antipsychotic drug action

Year	Major Advances
1950	Synthesis of chlorpromazine[3]
1952	Preliminary evidence of antipsychotic effect of chlorpromazine[6,7,11]
1958	Synthesis of haloperidol[16]
1960	Parkinson basal ganglia are deficient in dopamine[19]
1963	Neuroleptics raise level of monoamine metabolites[18]
1966	Neuroleptics may antagonize dopamine receptors[26]
1971	2 nmol haloperidol in plasma effective in psychosis[34]
1974	Synthesis of (+-) butaclamol[36]
1975	Tritiated haloperidol binds DA receptors[38]
1975	Effective neuroleptic dose correlates with D2 block[39]
1979	Multiple dopamine receptors[54]
1984	Bimodal D2 distribution in schizophrenia[45]
1984	High and low affinity states for D2[58]
1988	Cloning of the D2 receptor[63]
1988	In vivo imaging of D2 occupancy[47]
1990	Cloning of D3[67]
1999	Fast-off theory[71]
2000	Multiple genetic variants of D2 receptor[73-75]
2000	Impact of the D3 receptor[81]
2005	Impact of other neurotransmitter receptors[83]
2010	Impact of receptor heterodimers[85]
2017	Impact of D2 high affinity state[77]
2021	Structure and specificities of D1, D2 signaling complexes[79]