Add time:09/08/2019         Source:sciencedirect.com

The interaction of the formamidine pesticides chlordimeform (CDM) and amitraz (AMZ) with rat brain alpha2-adrenoceptors was investigated. Both compounds inhibited the binding of 3H-clonidine and 3H-yohimbine in vitro with IC50 values of 62–68 μM (CDM) and 95–110 nM (AMZ). In vivo administration of AMZ and CDM caused a dose-dependent inhibition of 3H-clonidine binding in rat forebrain. The inhibition was short-lasting (24 hr) following CDM administration, while after AMZ recovery of 3H-clonidine binding occurred only after 72 hr. Good correlations were found between inhibition of brain 3H-clonidine binding by the formamidines and “plasma equivalents” of these compounds and/or their biologically active metabolites, as measured by a new radioreceptor assay. These results suggest that 1) formamidines can interact in vivo with brain alpha2-adrenoceptors when administered at doses previously shown to cause toxic effects on the central nervous system: and 2) this effect is reversible, both in vivo and in vitro, and appears to be linked to the presence of the formamidines and/or their active metabolites at the receptor sites.

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