Do neuroleptics prevent the penetration of dopamine agonists into the brain?
A new, specific and highly sensitive method for the determination of apomorphine based on high performance liquid chromatography on a C18 reverse-phase column, coupled with electrochemical detection has been developed. The limit of detection of the assay is approximately 0.5 ng/sample (2 pmol). Haloperidol, cis-flupenthixol, metoclopramide and reserpine prevented the accumulation of apomorphine equally in "dopaminergic" as well as in "non-dopaminergic" brain areas. The non-neuroleptic trans-isomer of flupenthixol was without effect. Suppression of the accumulation of the dopamine agonist 6,7-ADTN (administered as the prodrug dibenzoyl-6,7-ADTN) was seen after combined treatment with haloperidol or reserpine, whereas cis- and trans-flupenthixol were without effect. The results imply that certain behavioural, biochemical and neuropharmacological studies, based on apomorphine in combination with other drugs, may need reinterpretation.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology*; D004347:Drug Interactions; D005260:Female; D051381:Rats; D013764:Tetrahydronaphthalenes / Q000378:metabolism; D013997:Time Factors
D014150:Antipsychotic Agents; D013764:Tetrahydronaphthalenes; D001058:Apomorphine; D004298:Dopamine