Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Molecules. 2020 Dec 25;26(1):70. doi: 10.3390/molecules26010070.

Alkaloids with Anti-Onchocercal Activity from Voacanga africana Stapf 
(Apocynaceae): Identification and Molecular Modeling.

Babiaka SB(1)(2), Simoben CV(3), Abuga KO(4), Mbah JA(1), Karpoormath R(5), 
Ongarora D(4), Mugo H(4), Monya E(6), Cho-Ngwa F(6), Sippl W(3), Loveridge 
EJ(7), Ntie-Kang F(1)(3)(8).

Author information:
(1)Department of Chemistry, Faculty of Science, University of Buea, P.O. Box 63, 
Buea CM-00237, Cameroon.
(2)AgroEco Health Platform, International Institute of Tropical Agriculture, 
Cotonou, Abomey-Calavi BEN-00229, Benin.
(3)Institute for Pharmacy, Martin-Luther-Universität Halle-Wittenberg, 
Kurt-Mothes-Str. 3, 06120 Halle, Germany.
(4)Department of Pharmaceutical Chemistry, School of Pharmacy, University of 
Nairobi, Nairobi P.O. Box 19676-00202, Kenya.
(5)Department of Pharmaceutical Chemistry, School of Chemistry, University of 
KwaZulu-Natal, Durban 4001, South Africa.
(6)ANDI Centre of Excellence for Onchocerciasis Drug Research, Biotechnology 
Unit, Faculty of Science, University of Buea, P.O. Box 63, Buea CM-00237, 
Cameroon.
(7)Department of Chemistry, Swansea University, Singleton Park, Swansea SA2 8PP, 
UK.
(8)Institute of Botany, Technical University of Dresden, 01217 Dresden, Germany.

A new iboga-vobasine-type isomeric bisindole alkaloid named voacamine A (1), 
along with eight known compounds-voacangine (2), voacristine (3), coronaridine 
(4), tabernanthine (5), iboxygaine (6), voacamine (7), voacorine (8) and 
conoduramine (9)-were isolated from the stem bark of Voacangaafricana. The 
structures of the compounds were determined by comprehensive spectroscopic 
analyses. Compounds 1, 2, 3, 4, 6, 7 and 8 were found to inhibit the motility of 
both the microfilariae (Mf) and adult male worms of Onchocerca ochengi, in a 
dose-dependent manner, but were only moderately active on the adult female worms 
upon biochemical assessment at 30 μM drug concentrations. The IC50 values of the 
isolates are 2.49-5.49 µM for microfilariae and 3.45-17.87 µM for adult males. 
Homology modeling was used to generate a 3D model of the O. ochengi thioredoxin 
reductase target and docking simulation, followed by molecular dynamics and 
binding free energy calculations attempted to offer an explanation of the 
anti-onchocercal structure-activity relationship (SAR) of the isolated 
compounds. These alkaloids are new potential leads for the development of 
antifilarial drugs. The results of this study validate the traditional use of V. 
africana in the treatment of human onchocerciasis.

DOI: 10.3390/molecules26010070
PMCID: PMC7795662
PMID: 33375687 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no conflict of interest.


2. Curr Med Chem. 2002 Oct;9(20):1807-18. doi: 10.2174/0929867023368980.

A review of chemical agents in the pharmacotherapy of addiction.

Levi MS(1), Borne RF.

Author information:
(1)Department of Medicinal Chemistry, School of Pharmacy, The University of 
Mississippi, University, MS 38677, USA.

Chemical substance abuse has tormented mankind throughout history. A number of 
chemical approaches have been employed in an attempt to treat chemical 
addiction. Unfortunately, most of these have proven unsuccessful though several 
chemical entities have been shown to be moderately effective. The naturally 
occurring alkaloid ibogaine has been reported to interrupt the cravings for 
alcohol, cocaine and opiates. Other alkaloids from Tabernanthe iboga, such as 
ibogamine and tabernanthine, provide insight into the structure activity 
relationship at the different receptors believed to be involved in addiction. 
The synthetic iboga alkaloid congener, 18-MC, also shows potential as an 
anti-addictive agent without the hallucinogenic effects of ibogaine. 
Additionally, acamprosate, BP 897, GBR12909, lofexidine and memantine have shown 
promising results in the treatment of addiction. All of these leads provide a 
start for the medicinal chemist to design anti-addictive agents, since currently 
no drugs are approved in the U.S. for the treatment of addictions to cocaine, 
methamphetamine, other stimulants or PCP.

DOI: 10.2174/0929867023368980
PMID: 12369879 [Indexed for MEDLINE]


3. Eur J Pharmacol. 1996 Aug 8;309(2):159-65. doi: 10.1016/0014-2999(96)00304-4.

Structurally modified ibogaine analogs exhibit differing affinities for NMDA 
receptors.

Layer RT(1), Skolnick P, Bertha CM, Bandarage UK, Kuehne ME, Popik P.

Author information:
(1)Laboratory of Neuroscience, National Institute of Diabetes, Digestive and 
Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0008, USA. 
rtlayer@helix.nih.gov

Based on both preclinical findings and anecdotal evidence in man, the 
psychoactive indole alkaloid ibogaine has been suggested to have anti-addictive 
properties. Previous studies indicate that blockade of NMDA receptors may 
mediate at least some of the putative anti-addictive actions of ibogaine. The 
potencies of a series of ibogaine analogs to inhibit 
(+)-[3-3H]5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10- imine 
([3H]MK-801) binding to NMDA receptors were examined. This series of analogs 
included the putative ibogaine metabolite O-desmethylibogaine, its metabolism 
resistant analog O-t-butyl-O-desmethylibogaine, the iboga alkaloids 
(+/-)-ibogamine, (+/-)-coronaridine, tabernanthine, harmaline, and the 
indolotropanes endo-3-(1-methylindol-2-yl)-8-methyl-8-azabicyclo[3.2.1]loctane 
(RS 075194-190), exo-3-(1-methylindol-2-yl)-8-methyl-8-azabicyclo[3.2.1]octane 
(RS 075237-190), and endo-3-(indol-2-yl)-8-methyl-8-azabicyclo[3.2.1]octane (RS 
025989-190). Among these compounds, ibogaine was the most potent inhibitor of 
[3H]MK-801 binding (Ki = approximately 1.2 microM), whilst the compounds with 
the greatest structural similarity to ibogaine, O-desmethylibogaine and 
O-t-butyl-O-desmethylibogaine were less potent (Ki = approximately 5.5 and 179.0 
microL, respectively). In morphine-dependent mice, ibogaine, but not 
O-desmethylibogaine or O-t-butyl-O-desmethylibogaine, attenuated naloxone 
precipitated withdrawal jumping. These findings are consistent with the 
hypothesis that inhibition of the expression of morphine dependence by ibogaine 
is related to its NMDA receptor antagonist properties.

DOI: 10.1016/0014-2999(96)00304-4
PMID: 8874134 [Indexed for MEDLINE]


4. Eur J Pharmacol. 1995 Jun 6;279(1):R1-3. doi: 10.1016/0014-2999(95)00247-i.

Ibogaine and its congeners are sigma 2 receptor-selective ligands with moderate 
affinity.

Bowen WD(1), Vilner BJ, Williams W, Bertha CM, Kuehne ME, Jacobson AE.

Author information:
(1)Laboratory of Medicinal Chemistry, National Institute of Diabetes and 
Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 
20892, USA.

Ibogaine (12-methoxyibogamine) exhibited moderate affinity for sigma 2 sites (Ki 
= 201 nM) and low affinity for sigma 1 sites (Ki = 8554 nM), thus showing 
43-fold selectivity for sigma 2 receptors. Tabernanthine (13-methoxyibogamine) 
and (+/-)-ibogamine had sigma 2 Ki = 194 nM and 137 nM, respectively. However, 
they showed 3- to 5-fold higher sigma 1 affinity compared to ibogaine, resulting 
in about 14-fold selectivity for sigma 2 sites over sigma 1. A potential 
ibogaine metabolite, O-des-methyl-ibogaine, had markedly reduced sigma 2 
affinity relative to ibogaine (Ki = 5,226 nM) and also lacked significant 
affinity for sigma 1 sites. (+/-)-Coronaridine ((+/-)-18-carbomethoxyibogamine) 
and harmaline (1-methyl-7-methoxy-3,4-dihydro-beta-carboline) lacked significant 
affinity for either sigma subtype. Thus, sigma 2 receptors could play a role in 
the actions of ibogaine.

DOI: 10.1016/0014-2999(95)00247-i
PMID: 7556375 [Indexed for MEDLINE]


5. Brain Res. 1994 Sep 19;657(1-2):14-22. doi: 10.1016/0006-8993(94)90948-2.

Effects of iboga alkaloids on morphine and cocaine self-administration in rats: 
relationship to tremorigenic effects and to effects on dopamine release in 
nucleus accumbens and striatum.

Glick SD(1), Kuehne ME, Raucci J, Wilson TE, Larson D, Keller RW Jr, Carlson JN.

Author information:
(1)Department of Pharmacology and Toxicology (A-136), Albany Medical College, NY 
12208.

Ibogaine, a naturally occurring alkaloid, has been claimed to be effective in 
treating addiction to opioid and stimulant drugs and has been reported to 
decrease morphine and cocaine self-administration in rats. The present study 
sought to determine if other iboga alkaloids, as well as the chemically related 
harmala alkaloid harmaline, would also reduce the intravenous 
self-administration of morphine and cocaine in rats. Because both ibogaine and 
harmaline induce tremors, an effect that may be causally related to 
neurotoxicity in the cerebellar vermis, the temorigenic activities of the other 
iboga alkaloids were assessed. Lastly, in view of the involvement of the 
dopaminergic mesolimbic system in the actions of drugs of abuse, the effects of 
some of the iboga alkaloids on extracellular levels of dopamine and its 
metabolites in the nucleus accumbens and striatum were determined. All of the 
tested alkaloids (i.e., ibogaine, tabernanthine, R- and S-coronaridine, R- and 
S-ibogamine, desethylcoronaridine, and harmaline) dose-dependently (2.5-80 
mg/kg) decreased morphine and cocaine intake in the hour after treatment; 
decreases in morphine and cocaine intake intake were also apparent the day after 
administration of some but not all of these alkaloids (i.e., ibogaine, 
tabernanthine, desethylcoronaridine, and the R-isomers of coronaridine and 
ibogamine). In some rats, there were persistent decreases in morphine or cocaine 
intake for several days after a single injection or after two or three weekly 
injections of one or another of these alkaloids; R-ibogamine produced such 
effects more consistently than any of the other alkaloids.(ABSTRACT TRUNCATED AT 
250 WORDS)

DOI: 10.1016/0006-8993(94)90948-2
PMID: 7820611 [Indexed for MEDLINE]