A preliminary TLC study of Tabernaemontana undulata, it's phytochemistry and possible psychopharmacology Tabernaemontana undulata has a long history of traditional use, nowdays most commonly known as it's use in Sananga, where the decoction of the root is used as an eye drop. The use of this plant for potential other CNS properties, or at doses above those administered in eye-drops, including for anti-addictive properties remains relatively unexplored. Likewise, the phytochemistry and psychopharmacology remains relatively unexplored with mixed findings. One source [1] claims that "22 different indole alkaloids have been described. Some of these alkaloids (i.e. conopharyngine, coronaridine, quebrachidine, voacangine and iso-voacangine) have shown analgesic, antimicrobial, CNS stimulant and diuretic activities (Bruneton et al., 1979; Ladhar et al., 1981; Van Beek and Verpoorte, 1985)". Some list ibogaine as a potential constituent in T. undulata but results have been very mixed. Conopharyngine Coronaridine Quebrachidine Voacangine Another [2] found the following constituents: Some T abernaemontana spp. have been found to have a similar phytochemical profile to Tabernanthe iboga [3] with Mexican species showing predominance of voacangine and ibogaine, or coronaridine and ibogamine while T. iboga in general shows ibogaine as the most abundant alkaloid, followed by constituents like iboxygaine, ibogaline, alloibogaine, catharanthine and ibogamine [4] but nonetheless there sometimes seems to be "phytochemical proximity between both genera". Coronaridine, along with stimulant effects, seems to potentially retain some of the anti- addictive effects of ibogaine [5], with activity on the autonomic and central nervous systems, acting as a painkiller and respiratory depressant and also being a potent AChE inhibitor. Voacangine exhibited a slight central nervous stimulant effect and similar anti- addictive properties to ibogaine itself, with potent AChE inhibitory properties and the likely mechanism of altering dopaminergic and glutamatergic signalling. Weak CNS stimulant 1 effects were noted from conopharyngine [6]. Tabernanthe iboga has been used in traditional medicine to combat fatigue, as a neuro- stimulant in rituals, and for treatment of diabetes. While cardiac side-effects [7] limited it's use, low doses were used in France as an antidepressant and current research indicates very low doses, potentially in synergy with conventional antidepressants, may lead to therapeutic synergy in the treatment of mental health conditions [8] with combinations of low doses ibogan-type alkaloids (0.01 − 2.0 mg/kg) and antidepressants proposed to "produce a synergistic effect in reducing symptoms of psychiatric disorders such as bipolar disorder, depression, schizophrenia, paranoia, anxiety, panic disorder, mania, post- traumatic stress disorder (PTSD), and obsessive − compulsive disorder... [providing a] highly efficient therapeutic responses compared to when each of the active agents is used alone" "The major mechanism of action of ibogaine appears to be its ability to bind to multiple binding sites within the central nervous system (CNS), such as N-methyl-D- aspartate (NMDA), receptor coupled ion channels, κ-opioid (κ1 and κ2), μ-opioid and σ2, serotonin (5-HT2 and 5-HT3), muscarinic (M1 and M2) receptors, monoamine oxidase receptors, and nicotinic acetylcholine receptors (Maciulaitis et al., 2008). Ibogaine activates the glial cell line—derived neurotrophic factor (GDNF) pathway..." Initially, TLC (silica, glass backed, 0.2mm, I 2 visualisation) with acetone elution gave significant trailing and poor separation of the constituents for T. undulata . Elution with acetone:white spirits 1:1 gave some separations of compounds from T. undulata (basified iPrOH extract, crude initial Rf = 0.13, 0.35, 0.56, 0.89). A mixed solvent of acetone:white spirits 1:1 was selected as optimal extraction solvent for the plant material after it had been basified with aq. ammonia. Good resolution of the constitutents was seen after I 2 visualisation using the same solvent for TLC elution. 2 TU Tabernaemontana undulata root bark TLC with I 2 visualisation and UV Major constituents in T. undulata root bark were at Rf = 0.69, 0.62, 0.52, 0.48 and 0.38. A reference sample of T. iboga (TI) was used for comparison with Rf's obtained of 0.62 (major), 0.52 and 0.38, with lesser minor constituents. A similar constituent Rf = 0.62 was seen for both T. undulata and T. iboga , in the latter it was the predominate constituent and assumed to be the predominate alkaloid, ibogaine. That said, this constituent was much less present in T. undulata and noting the structural similarity of ibogan-type monoterpene indole alkaloids, some may share similar Rf values. Many of the constituents showed strong UV fluorescence. 3 References: [1] Jaume Sanz-Biset, Salvador Cañigueral, Plant use in the medicinal practices known as “strict diets” in Chazuta valley (Peruvian Amazon), Journal of Ethnopharmacology, Volume 137, Issue 1, 2011, Pages 271-288, https://doi.org/10.1016/j.jep.2011.05.021 [2] Van Beek TA, Verpoorte R, Svendsen AB, Leeuwenberg AJ, Bisset NG. Tabernaemontana L. (Apocynaceae): a review of its taxonomy, phytochemistry, ethnobotany and pharmacology. J Ethnopharmacol. 1984 Feb;10(1):1-156. https://doi.org/10.1016/0378-8741(84)90046-1 [3] Krengel, F., Chevalier, Q., Dickinson, J., Santoyo, J. H., & Reyes-Chilpa, R. (2019). 4 Metabolite Profiling of Antiaddictive Alkaloids from Four Mexican Tabernaemontana Species and the Entheogenic African Shrub Tabernanthe iboga (Apocynaceae). Chemistry & Biodiversity. https://doi.org/10.1002/cbdv.201800506 [4] Bading-Taika, B., Akinyeke, T., Magana, A. A., Choi, J., Ouanesisouk, M., Torres, E. R. S., ... Stevens, J. F. (2018). Phytochemical characterization of Tabernanthe iboga root bark and its effects on dysfunctional metabolism and cognitive performance in high-fat-fed C57BL/6J mice. Journal of Food Bioactives, 3, 111–123. https://doi.org/10.31665/JFB.2018.3154 [5] Glick SD, Kuehne ME, Raucci J, Wilson TE, Larson D, Keller RW Jr, Carlson JN. 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. Brain Res. 1994 Sep 19;657(1-2):14-22. doi: 10.1016/0006-8993(94)90948-2. https://doi.org/10.1016/0006-8993(94)90948-2 [6] Carroll PR, Starmer GA. Studies on the pharmacology of conopharyngine, an indole alkaloid of the voacanga series. Br J Pharmacol Chemother. 1967 May;30(1):173-85. https://doi.org/10.1111%2Fj.1476-5381.1967.tb02123.x [7] Koenig, Xaver, and Karlheinz Hilber. The anti-addiction drug ibogaine and the heart: a delicate relation. Molecules 20.2 (2015): 2208-2228. https://www.mdpi.com/1420-3049/20/2/2208 [8] Robert B. Kargbo. Ibogaine and Their Analogs as Therapeutics for Neurological and Psychiatric Disorders ACS Medicinal Chemistry Letters 2022 13 (6), 888-890 . https://doi.org/10.1021/acsmedchemlett.2c00214 5