5HT2 binding sites after mianserin: comparison of loss of sites and brain levels of drug.

The purpose of this study was to evaluate the role of residual drug in mediating the loss of 5HT2 binding sites after in vivo treatment with mianserin. Brain levels of mianserin were measured using a radioreceptor assay and compared with the extent of receptor loss. Peak brain levels were found within 0.5 to 1 h after dosing and the drug disappeared from brain with a half-life of 1-3 h. A dissociation was found between the levels of mianserin and the loss of binding sites. At the time of peak drug levels, the density of 5HT2 sites was not changed, while 24 h later, a significant loss of sites was evident. Although some drug-related material remained in the brain at 24 h after treatment, there was no apparent relationship between the regional distribution of residual drug and the distribution of 5HT2 binding sites. Studies with [3H]mianserin confirmed these results. Furthermore, incubation of brain slices with mianserin did not lead to a decrease in 5HT2 binding site density, consistent with the conclusion that the in vivo effects of the drug do not reflect a direct action.