N-PHTHALIMIDOALKYL DERIVATIVES OF 2-BETA-CARBOMETHOXY-3-BETA-(4'-IODOPHENYL)TROPANE (BETA-CIT) - BRAIN MONOAMINE TRANSPORTER AFFINITY

A series of novel N-phthalimidoalkyl analogs of the stable phenyltropa ne beta-CIT were synthesised and evaluated by selective radioligand bi nding assays for affinity to transporters for dopamine (DA), serotonin (5-HT) and norepinephrine (NE) in corpus striatum tissue from rat for ebrain. beta-CIT and novel compounds with the phthalimido moiety separ ated by greater than or equal to 4 methylene groups from the nitrogen atom of the tropane ring (6-8) showed similarly greater affinity at 5- HT than DA transporters; this affinity was last with only 2 or 3 carbo n atoms (4 and 5). These results are consistent with interference at a critical binding site for the tropane nitrogen on the transporter pro teins and indicate that the tropane nitrogen atom can be substituted w ith large substituted alkyl moieties without loss of affinity or selec tivity for amine transporters. (C) 1997, Elsevier Science Ltd.