Synthesis and biological evaluation of a series of novel N- or O-fluoroalkyl derivatives of tropane: potential positron emission tomography (PET) imaging agents for the dopamine transporter.

A series of novel fluoroalkyl-containing tropane derivatives was synthesized, and their binding affinities for the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) were determined via competitive binding assays. Among these derivatives, the fluoropropyl ester of beta-CIT (19), the fluoroethyl ester of beta-CIT (20), the N-fluoropropyl derivative of beta-CBT (12), and the fluoropropyl ester of beta-CMT (18) displayed higher affinity and greater selectivity for the DAT versus SERT and NET than FP-CIT, which indicates that they are attractive candidates for the development of (18)F-labeled PET imaging agents for the DAT.

Plasma levels of apomorphine following intravenous, intraperitoneal and oral administration to mice and rats.

Clinical use of the potent dopaminergic partial-agonist apomorphine (APO) in a wide variety of neuropsychiatric disorders is hampered by a lack of data concerning tissue/plasma levels following various routes of administration. In the present experiments, plasma levels were assessed at various times up to 4 hours after APO administration IV, IP, and PO to mice and rats. Plasma levels of total radioactivity after PO administration of [3H]-APO were 50 to 65% of those seen after IV administration, but brain levels were almost undetectable after PO administration. Organic solvent-extractable concentrations of tritium-labelled material after IV and IP administration of [3H]-APO to mice were significantly lower than the levels of total radioactivity, while after PO administration, these concentrations were minimal. Similar results were observed in rats following IV and PO administration of [3H]-APO.