Inhibition of choline uptake by N-cyclohexylcholine, a high affinity ligand for the choline transporter at the blood-brain barrier.

Article Details

Citation

Geldenhuys WJ, Lockman PR, Philip AE, McAfee JH, Miller BL, McCurdy CR, Allen DD

Inhibition of choline uptake by N-cyclohexylcholine, a high affinity ligand for the choline transporter at the blood-brain barrier.

J Drug Target. 2005 May;13(4):259-66.

PubMed ID
16051538 [ View in PubMed
]
Abstract

The blood-brain barrier (BBB) choline transporter (CHT) may have utility as a drug delivery vector for drugs that act in the central nervous system. Previous studies suggested the importance of hydrophobic moieties on the cationic nitrogen of choline for improved affinity for this transporter. In a pilot study, we therefore designed five novel N-cycloalkyl derivatives of choline, one of which showed promising inhibition properties. This choline analogue had a cyclohexyl (UMBB-5) moiety substituting one of the methyl groups attached to the cationic nitrogen in choline. In situ experimental data were obtained from in situ rat brain perfusion studies. The binding affinity for the BBB-choline transporter found for UMBB-5 was K(i)=1.9 microM. Comparative molecular field analysis (CoMFA) suggested that the cyclohexyl moiety orientates towards a steric favourable area. Taken together, the results of these in situ and in silico studies provide further evidence or restrictions that occur with binding to this brain drug delivery vector.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
CholineHigh affinity choline transporter 1ProteinHumans
Unknown
Substrate
Details
Choline salicylateHigh affinity choline transporter 1ProteinHumans
Unknown
Substrate
Details