Karen K. Szumlinski^(1)
(1)Albany Medical College - Albany. United States

	[Neuroscience]	[Pharmacology]	[Psychiatry]

INTRODUCTION

18-Methoxycoronaridine (18-MC) fig. 1 is a synthetic iboga alkaloid congener, derived from the putative anti-addictive drug, ibogaine (IBO), developed with the goal of making available a safer IBO-like anti-addictive agent. Similar to IBO ⁽¹⁾, 18-MC decreases the self-administration of a variety of drugs [incl., morphine (MOR), cocaine (COC), nicotine and alcohol] and blocks some of the acute signs of MOR withdrawal in rats ^(2,3). In contrast to IBO ⁽¹⁾, 18-MC is non-tremorigenic and does not produce cerebellar toxicity, induce bradycardia or attenuate responding for water ^(2,3). The binding profile for 18-MC is slightly different from that of IBO; IBO binds to mu and kappa opioid receptors, the NMDA receptor, the 5-HT3 receptor and the serotonin transporter ^(1,4), where 18-MC shows moderate binding affinity for all three known opioid receptors (mu, delta and kappa) and the 5-HT3 receptor ^(2,3).

The repeated, intermittent administration of stimulant and opioid drugs produces a progressive increase in the behavioural, and often the neurochemical, effects of these drugs ^(5,6). Termed sensitization ⁽⁶⁾, this phenomenon is theorized to lie at the core of drug craving and relapse in drug addiction ⁽⁷⁾. Thus, the possibility exists that IBO and related iboga agents, such as 18-MC, interrupt the psychological and physiological aspects of addiction by modulating the expression of sensitization. Studies to date demonstrated that pretreatment (19 h earlier) with IBO increases the dopamine (DA) response in the nucleus accumbens (NAC) to an acute injection of COC ⁽¹⁾ and decreases the DA response to an acute injection of MOR ⁽¹⁾. This latter effect is greater in MOR-experienced rats ⁽⁸⁾. Consistent with these neurochemical findings, previous IBO studies demonstrated that IBO (19 h earlier) increases the potency of COC to induce locomotor responding ^(1,9-10) and enhances the expression of COC-induced stereotypy ⁽¹¹⁾ in both acute and chronic COC-treated rats. IBO also decreases the locomotor responses to an acute injection of MOR ^(1,12) and this effect is greater in MOR-experienced rats ⁽¹²⁾. Studies of 18-MC to date indicate that 18-MC shares some of these DA and locomotor effects of IBO; 18-MC (19 h earlier) decreases the increase in NAC DA induced by acute MOR ⁽²⁾ and increases the locomotion induced by an acute injection of COC ^(2,3). Given the similar efficacies of IBO and 18-MC on drug self-administration ⁽³⁾, a series of studies determined the effects of 18-MC on the sensitization of DA treansmission in the NAC and on the expression of sensitization of behaviours putatively mediated by DA sensitization (i.e., locomotion and stereotypy) following chronic treatment with MOR, COC or SAL.

Discussion Board

Any Comment to this presentation?

[ABSTRACT] [INTRODUCTION] [MATERIALS AND METHODS] [RESULTS] [FIGURES] [FIGURES-2] [DISCUSSION] [CONCLUSIONS] [ACKNOWLEDGEMENTS] [REFERENCES] [Discussion Board]

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	[Neuroscience]	[Pharmacology]	[Psychiatry]

Karen K. Szumlinski
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Last update: 18/01/00