Copyright ©The Author(s) 2021.
World J Psychiatr. Jul 19, 2021; 11(7): 355-364
Published online Jul 19, 2021. doi: 10.5498/wjp.v11.i7.355
Table 1 Major steps in the dopamine hypothesis of antipsychotic drug action
Major Advances
1950Synthesis of chlorpromazine[3]
1952Preliminary evidence of antipsychotic effect of chlorpromazine[6,7,11]
1958Synthesis of haloperidol[16]
1960Parkinson basal ganglia are deficient in dopamine[19]
1963Neuroleptics raise level of monoamine metabolites[18]
1966Neuroleptics may antagonize dopamine receptors[26]
19712 nmol haloperidol in plasma effective in psychosis[34]
1974Synthesis of (+-) butaclamol[36]
1975Tritiated haloperidol binds DA receptors[38]
1975Effective neuroleptic dose correlates with D2 block[39]
1979Multiple dopamine receptors[54]
1984Bimodal D2 distribution in schizophrenia[45]
1984High and low affinity states for D2[58]
1988Cloning of the D2 receptor[63]
1988In vivo imaging of D2 occupancy[47]
1990Cloning of D3[67]
1999Fast-off theory[71]
2000Multiple genetic variants of D2 receptor[73-75]
2000Impact of the D3 receptor[81]
2005Impact of other neurotransmitter receptors[83]
2010Impact of receptor heterodimers[85]
2017Impact of D2 high affinity state[77]
2021Structure and specificities of D1, D2 signaling complexes[79]