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A number of hypotheses have been proposed to explain why levamisole is used as an adulterant. Here, we examined whether levamisole might enhance acute pharmacological effects of cocaine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Levamisole and its phase I metabolites were tested for in vitro activity at monoamine receptors and transporters. The effect of levamisole (0.1\u201310 \u00b5M) on cocaine-induced inhibition of [\n                      <jats:sup>3<\/jats:sup>\n                      H]dopamine uptake was examined in rat brain synaptosomes. In vivo microdialysis in nucleus accumbens of male rats was employed to determine neurochemical effects of cocaine (1\u20133\u00a0mg\/kg, intravenous), in the absence or presence of levamisole (1:1 ratio with cocaine).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Levamisole displayed no measurable activity at monoamine receptors or transporters. The metabolite aminorex acted as a potent substrate at transporters for dopamine, norepinephrine and serotonin, whereas rexamino had affinity for adrenoreceptors and weak substrate activity at norepinephrine transporters. Levamisole did not alter cocaine-induced inhibition of dopamine uptake in vitro. Administration of cocaine, or cocaine plus levamisole, produced similar increases in extracellular dopamine and locomotor stimulation in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We found no evidence that levamisole alters the acute pharmacological effects of cocaine in male rats. The metabolite aminorex is a potent monoamine transporter substrate which could contribute to effects of levamisole under certain conditions (e.g., repeated, high-dose exposure), but most studies in human users of levamisole-adulterated cocaine have failed to detect measurable quantities of aminorex.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00213-026-07145-1","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T02:11:43Z","timestamp":1789006303000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuropharmacology of levamisole and its phase I metabolites: lack of evidence for levamisole-cocaine interactions"],"prefix":"10.1007","author":[{"given":"Dorota","family":"Zolkowska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt R.","family":"Lehner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Partilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce E.","family":"Blough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Baumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"7145_CR1","first-page":"137","volume":"4","author":"JG Adams","year":"1978","unstructured":"Adams JG (1978) Pharmacokinetics of levamisole. 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