Although the
alkaloid ibogaine is a potent
hallucinogenic agent some indications suggest that it may be useful for the treatment of
opioid and
cocaine addiction. The neurochemical mechanism(s) underlying
ibogaine effects remain unclear. In the present study we investigated the interaction of
ibogaine with the
phencyclidine (PCP) site located in the
ionophore of the
N-methyl-D-aspartate (
NMDA) receptor complex, with the
NMDA receptor binding site, and with sigma binding sites. In well-washed membrane preparations of rat cortex and cerebellum, the PCP sites were labeled with [3H]
MK-801 or [3H]1-[1(2-theinyl)-cyclohexyl]-
piperidine ([3H]TCP), and the
NMDA receptor with [3H]-
CGP 39653. The sigma-1 and sigma-2 binding site in rat cortex and cerebellum were labeled with [3H]
pentazocine and [3H]1,3-di-o-tolyl-
guanidine ([3H]DTG), respectively. Results indicated that
ibogaine interacts with high- and low-affinity PCP binding sites in the cortex: Ki(H) = 0.01-0.05 microM; Ki(L) = 2-4 microM, and only with low-affinity sites in the cerebellum: Ki = 2-4, microM. In contrast,
ibogaine (> 100 microM) had no affinity for [3H]-
CGP 39653 binding sites (cortex and cerebellum). The affinity of
ibogaine for sigma-1 and -2 binding sites in cortex and cerebellum ranged from 1.5-3 microM. Since
NMDA receptor antagonists (e.g., MK-801) are thought to attenuate
opioid withdrawal symptoms and
cocaine sensitization, it is possible that binding of
ibogaine to the PCP sites contributes to its potential '
endabuse' properties. In turn,
ibogaine interaction with sigma binding sites may be associated with its adverse effects.