Background: Risperidone is an antipsychotic drug. In blood, this drug
binds mainly to human serum albumin (HSA) and is also transported by HSA.
Method: To study certain details of the interaction between risperidone and HSA, a
fluorescent dye CAPIDAN was used as a reporter. This dye specifically fluoresces
from HSA in serum and is highly sensitive to structural changes in HSA including
pathology-induced changes. Interaction of CAPIDAN with HSA has been studied using
time-resolved fluorescence techniques.
Result: The addition of phenylbutazone, a marker for the HSA drug-binding site I,
leads to displacement of CAPIDAN from this site due to direct competition between
phenylbutazone and the dye. The addition of risperidone induces a response of CAPIDAN
fluorescence that is highly similar to its response to phenylbutazone. This response
depends strongly on ionic strength and is very similar in both cases, phenylbutazone
and risperidone. This similarity suggests that risperidone binds to HSA in
the region of site I. In this site, the risperidone molecule probably covers the positive
charge of Arginine 218 or Arginine 222 preventing their interaction with the CAPIDAN
negatively charged carboxyl group. This effect was observed both in isolated
HSA and in serum, suggesting similarity of the interaction.
Conclusion: Thus, risperidone is able to prevent binding of organic anions (i.e.
CAPIDAN as a drug-like molecule) to HSA.