4,5,9,10-Tetrahydro-1,4-ethanobenz[b]quinolizine as a Prodrug for Its Quinolizinium Cation as a Ligand to the Open State of the TCP-Binding Site of NMDA Receptors

A new derivative of 4,5,9,10-tetrahydro-1,4-ethanobenz[b]quinolizine (2) has been designed as a prodrug for its quinolizinium cation (1) that is a potent antagonist of the TCP-binding site of NMDA receptors at the open state. The 11C-labeled 2 showed high accumulation of radioactivity in the brain in an in vivo biodistribution study. The speculation of 2 as a prodrug of 1 has been proven by the fact that 1 was observed in a high ratio to 2 in an analysis by RP-HPLC of the brain homogenates. 2001 Elsevier Science Ltd. All rights reserved

Synthesis and Evaluation of 18F-and 11C-Labelled 9,10-Ethanobenzo[b]quinolizinium Derivatives for Imaging of the NMDA Receptor at the TCP-Binding Site

Derivatives of 9,10-ethanobenzo[b]quinolizinium are potent antagonists of the TCP-site of the NMDA receptor. Two fluoroethyl-substituted analogues were labelled with fluorine-18 by displacement of the tosylate with [18F]fluoride, followed by a Diels-Alder reaction. A methoxy-substituted analogue labelled with carbon-11 was obtained by O-methylation of the corresponding hydroxy precursor with [11C]iodomethane. In biodistribution studies in mice with these three radioligands, it was found that they have little ability to penetrate the blood-brain barrier