{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:34:35Z","timestamp":1791088475653,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,10,12]],"date-time":"2004-10-12T00:00:00Z","timestamp":1097539200000},"content-version":"vor","delay-in-days":4090,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Synapse"],"published-print":{"date-parts":[[1993,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The purpose of this study was to determine whether dopamine D4 receptors could be detected in the human brain striatum by means of an indirect ligand\u2010binding method, because no dopamine D4 receptor\u2010selective ligand presently exists. The antipsychotic clozapine is more selective for the dopamine D4 receptor than for other dopamine receptors. Although most antipsychotic drugs act in the striatum to elicit Parkinson\u2010like side\u2010effects, clozapine is atypical in that it does not produce Parkinsonism. To understand this atypical action of clozapine, it would be helpful to know whether the presumed target for clozapine, the dopamine D4 receptor, is or is not present in the human striatum. We measured dopamine D4 receptors indirectly, using [<jats:sup>3<\/jats:sup>H]emonapride<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"#note1\"\/><jats:fn><jats:p>Emonapride (or YM\u201009151\u20102; eis\u2010N\u2010[(2RS,3RS)\u2010l\u2010benzyl\u20102\u2010methylpyrrolin\u2010 3\u2010yll\u20105\u2010chloro\u20102\u2010methoxy\u20104\u2010\u223cmethylamino\u2010benzamide]) contains two asymmetric carbon atoms and is, therefore, a racemate of four enantiomers, two of which, (R,R)YM\u2010O9151\u20102 and (S,S)YM\u201009151\u20102, are active with identical potency (see Refs. in Seeman et al., 1992).<\/jats:p><\/jats:fn>\n and [<jats:sup>3<\/jats:sup>H]raclopride. Emonapride has a high affinity (K = 90 pM) for the dopamine D4 receptor, while raclopride has a very low affinity for this receptor (K = 240 nM); thus, any difference in the densities of these two [<jats:sup>3<\/jats:sup>H]ligands (in the absence of dopamine) could be attributed to the presence of dopamine D4 receptors. Since the binding of [<jats:sup>3<\/jats:sup>H]raclopride is sensitive to endogenous dopamine, we used Parkinson\u2010diseased tissue which has little dopamine. We found that the densities of the two ligands were identical in Parkinson striata, indicating a low density (&lt;1 pmol\/g) for dopamine D4 receptors in the human striatum. This low or undetectable density of dopamine D4 receptors in the striatum is consistent with other data indicating that clozapine does not have its major action in the human striatum. Thus, the atypical action of clozapine, insofar as clozapine does not elicit Parkinson side\u2010effects, may be based on its ability to avoid striatal dopamine D2 receptors and to target dopamine D4 receptors in non\u2010striatal brain regions. In schizophrenia striata the density of [<jats:sup>3<\/jats:sup>H]emonapride was almost two\u2010fold higher than that of [<jats:sup>3<\/jats:sup>H]raclopride. Considering that there are few dopamine D4 receptors in the human striatum, this two\u2010fold difference is best explained by endogenous dopamine interfering with the binding of [<jats:sup>3<\/jats:sup>H]raclopride, but not that of [<jats:sup>3<\/jats:sup>H]emonapride. \u00a9 1993 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/syn.890140402","type":"journal-article","created":{"date-parts":[[2004,12,31]],"date-time":"2004-12-31T22:19:24Z","timestamp":1104531564000},"page":"247-253","source":"Crossref","is-referenced-by-count":41,"title":["Low density of dopamine D4 receptors in Parkinson's, schizophrenia, and control brain striata"],"prefix":"10.1002","volume":"14","author":[{"given":"Philip","family":"Seeman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010Chang","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert H. 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