Iboga alkaloids Ibogaine

Ion channels Ibogaine and other iboga alkaloids have micromolar affinity for voltage gated Nan-channels (Deecher et al. 1992). Tabernanthine is also a Ca2-i- channel blocker, producing half-maximal inhibition in the micromolar range (7-21 pM) (Miller and Godfraind 1983). 

Alternative iboga alkaloids Potential neurotoxic effects of ibogaine have raised concern over its clinical use. It is possible that the antiaddictive and neurotoxic actions of ibogaine are discrete, allowing for potential separation of clinical and toxic effects (Molinari et al. 1996). Some other iboga alkaloids may have these properties, such as 18-MC. 

MC is a synthetic iboga alkaloid that may retain ibogaine s antiaddictive effects, but lack the effects of neurotoxicity and tremor (Click... 

Other iboga alkaloids besides ibogaine (tabernanthine, R- and S-coronaridine, R- and S-ibogamine, and desethylcoronaridine) decrease morphine and cocaine intake in animals shortly after administration, and in some cases one day after administration (Click et al. 1994). R-ibogamine was the most consistent in this effect, reducing intake for several days after a single injection. 

Ibogaine has demonstrated toxic effects, which could potentially limit its usefulness in treating addiction. However, the proper dosage of alternative iboga alkaloids may avert this problem. The median lethal dose of ibogaine is 82 mg/kg in the guinea pig and 327 mg/kg in the rat (Dhahir 1971 Delourme-Houde 1946). Use of ibogaine for addiction treatment has been associated with two deaths overseas. 

Cluster 8 Iboga and Ibogaine, the bush from Africa used in initiatory rites and by hunters to produce extended stillness, and its principal alkaloid that produces vivid imagery and stimulation... 

Although the isolation of the principal alkaloid, ibogaine, of Taber-nanthe iboga was described at the turn of the present century (1), it was not until the early 1950 s that serious work on its structure was begun. It had been shown to contain a methoxy group and, by means of color reactions (19) and by measurement of its UV-spectrum, to be an indole (20), but it was not recognized to be a methoxyindole until permanganate oxidation was found to afford 5-methoxy-A-oxalylanthranilic acid (21). 

Details have been published of the total syntheses of velbanamine, isovel-banamine, cleavamine, 18/3-carbomethoxycleavamine, and catharanthine. Rosen-mund s route to the iboga alkaloids has now been appropriately modified to yield ibogamine and ibogaine, in addition to epi-ibogamine, and details of this work are also available. Hydroboration-oxidation of (227), presumably obtained by a thio-Claisen rearrangement [cf. (200)- (201)] affords the alcohol (228) which is a key intermediate in a Kutney-type synthesis of cleavamine however, details of the synthesis are not yet available. ... 

Taylor in 1957 (47) [see also Taylor (12,13)]. Total synthesis from nicotinamide was reported using a 13- (48) or 14-step (49) sequence. The 13C NMR spectra of several iboga alkaloids were published in 1976 (50). The synthesis of tritiated ibogaine was recently reported (51,52). 

Glick et al. (96) demonstrated that ibogaine and several iboga alkaloids (tabernanthine, R- and 5-coronaridine, R- and 5-ibogamine, desethylcoro-naridine, and harmaline) reduced cocaine self-administration in rats in a dose-related fashion (2.5-80 mg/kg). For some alkaloids, these effects were seen the day after injection. O-Desmethylibogaine (40 mg/kg) (89) and 18-methoxycoronaridine (97) were also reported to inhibit cocaine selfadministration. 

Iberin, Z8 Ibogaine, KIS Iboga alkaloids, KIS Ibogamine, KIS Ichangin, TS2 Ichthyothereol, YIS Iditol, Cl Idose, Cl Illudin S, T30 Illudol, T30... 

Iboga ibogaine, 768 Ignatius beans, 553 llligera spp., 319 Imperialine, 732 Indaconitine, 673, 684 Indole alkaloids, 484 Indolizine, 16 Insularine, 362, 370... 

Further variants on the terpenoid indole alkaloid skeleton (Figure 6.82) are found in ibogaine from Tabemanthe iboga, vincamine from Vinca minor, and ajmaline from Rauwolfia serpentina. Ibogaine is simply a C9 Iboga type alkaloid, but is of interest as an experimental drug to treat heroin addiction. In a number of European countries, vincamine is used clinically as a vasodilator to increase cerebral blood flow in cases of senility, and ajmaline for cardiac arrhythmias. Ajmaline... 

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