Worldwide, there are plants known as psychoactive plants that naturally contain psychedelic active components. They have a high concentration of neuroprotective substances that can interact with the nervous system to produce psychedelic effects. Despite these plants' hazardous potential, recreational use of them is on the rise because of their psychoactive properties. Early neuroscience studies relied heavily on psychoactive plants and plant natural products (NPs), and both recreational and hazardous NPs have contributed significantly to the understanding of almost all neurotransmitter systems. Worldwide, there are many plants that contain psychoactive properties, and people have been using them for ages. Psychoactive plant compounds may significantly alter how people perceive the world.
1. J Biol Chem. 2019 Jun 28;294(26):10336-10348. doi: 10.1074/jbc.RA119.008848. Epub 2019 May 20. Mitochondrially targeted cytochrome P450 2D6 is involved in monomethylamine-induced neuronal damage in mouse models. Chattopadhyay M(1), Chowdhury AR(1), Feng T(1), Assenmacher CA(2), Radaelli E(2), Guengerich FP(3), Avadhani NG(4). Author information: (1)From the Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104. (2)the Department of Pathobiology, MJR-VHUP, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, and. (3)the Department of Biochemistry, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232. (4)From the Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, narayan@vet.upenn.edu. Parkinson's disease (PD) is a major human disease associated with degeneration of the central nervous system. Evidence suggests that several endogenously formed 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mimicking chemicals that are metabolic conversion products, especially β-carbolines and isoquinolines, act as neurotoxins that induce PD or enhance progression of the disease. We have demonstrated previously that mitochondrially targeted human cytochrome P450 2D6 (CYP2D6), supported by mitochondrial adrenodoxin and adrenodoxin reductase, can efficiently catalyze the conversion of MPTP to the toxic 1-methyl-4-phenylpyridinium ion. In this study, we show that the mitochondrially targeted CYP2D6 can efficiently catalyze MPTP-mimicking compounds, i.e. 2-methyl-1,2,3,4-tetrahydroisoquinoline, 2-methyl-1,2,3,4-tetrahydro-β-carboline, and 9-methyl-norharmon, suspected to induce PD in humans. Our results reveal that activity and respiration in mouse brain mitochondrial complex I are significantly affected by these toxins in WT mice but remain unchanged in Cyp2d6 locus knockout mice, indicating a possible role of CYP2D6 in the metabolism of these compounds both in vivo and in vitro These metabolic effects were minimized in the presence of two CYP2D6 inhibitors, quinidine and ajmalicine. Neuro-2a cells stably expressing predominantly mitochondrially targeted CYP2D6 were more sensitive to toxin-mediated respiratory dysfunction and complex I inhibition than cells expressing predominantly endoplasmic reticulum-targeted CYP2D6. Exposure to these toxins also induced the autophagic marker Parkin and the mitochondrial fission marker Dynamin-related protein 1 (Drp1) in differentiated neurons expressing mitochondrial CYP2D6. Our results show that monomethylamines are converted to their toxic cationic form by mitochondrially directed CYP2D6 and result in neuronal degradation in mice. © 2019 Chattopadhyay et al. DOI: 10.1074/jbc.RA119.008848 PMCID: PMC6664168 PMID: 31113867 [Indexed for MEDLINE] Conflict of interest statement: The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health 2. Talanta. 2011 Jan 15;83(3):717-23. doi: 10.1016/j.talanta.2010.10.012. Epub 2010 Oct 14. Stability-indicating high performance liquid chromatographic determination of raubasine in its binary mixture with kinetic study of raubasine acid degradation. El-Sayed MA(1). Author information: (1)Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, P.O. Box 715, Makkah, Saudi Arabia. boodim3@yahoo.com Erratum in Talanta. 2011 Mar 15;84(1):244. Stability-indicative determination of raubasine (RAB) in the presence of its degradate and its binary mixture with almitrine dismesylate (ALM) was investigated. The degradation product had been isolated, via acid-degradation, characterized and confirmed. Selective quantification of RAB and ALM in bulk form, pharmaceutical formulations and/or in the presence of RAB degradate was demonstrated. The analytical technique adopted for quantification was high performance liquid chromatography (HPLC). Separation was performed using a ZORBAX ODS column with a mobile phase consisting of acetonitrile+phosphate buffer pH 3.4 80:20 (v/v) with UV detection at 254 nm. The method showed high sensitivity with good linearity over the concentration range of 5-120 and 5-60 μg mL(-1) for RAB and ALM respectively. The HPLC method was used to study the kinetics of RAB acid degradation that was found to follow a first-order reaction. The activation energy could be estimated from the Arrhenius plot and it was found to be 18.152 kcal mol(-1). Copyright © 2010 Elsevier B.V. All rights reserved. DOI: 10.1016/j.talanta.2010.10.012 PMID: 21147311 [Indexed for MEDLINE] 3. J Pharm Biomed Anal. 2010 Jan 5;51(1):65-9. doi: 10.1016/j.jpba.2009.08.005. Epub 2009 Aug 12. Simple and reproducible HPLC-DAD-ESI-MS/MS analysis of alkaloids in Catharanthus roseus roots. Ferreres F(1), Pereira DM, Valentão P, Oliveira JM, Faria J, Gaspar L, Sottomayor M, Andrade PB. Author information: (1)Department of Food Science and Technology, CEBAS (CSIC), Murcia, Spain. Catharanthus roseus is one of the most important medicinal plants worldwide. The leaves of this species are the only source of the indolomonoterpenic alkaloids vincristin (leurocristine) and vinblastin (vincaleucoblastine), whose anticancer activity represents powerful therapeutics to many diseases, such as Hodgkin lymphoma. Usually, the remaining plant parts go to waste. Here we describe a phytochemical study on this species roots. Alkaloids in aqueous extracts, the usual form of consumption of this matrix, were studied using HPLC-DAD-ESI-MS/MS, which allowed the identification of 19-S-vindolinine, vindolinine, ajmalicine and an ajmalicine isomer, tabersonine, catharanthine, serpentine and a serpentine isomer. Quantification of the identified compounds revealed that serpentine and its isomer were predominant (64.7%) over the other alkaloids, namely vindolinine and its isomer (23.9%), catharanthine (7.7%) and ajmalicine (3.8%). The used procedure revealed to be simple, sensitive and reproducible. DOI: 10.1016/j.jpba.2009.08.005 PMID: 19720492 [Indexed for MEDLINE] 4. Drug Metab Dispos. 1994 Nov-Dec;22(6):916-21. In vitro metabolism of dorzolamide, a novel potent carbonic anhydrase inhibitor, in rat liver microsomes. Hasegawa T(1), Hara K, Kenmochi T, Hata S. Author information: (1)Development Research Laboratories, Banyu Pharmaceutical Co. Ltd, Saitama, Japan. The in vitro metabolism of dorzolamide, a potent carbonic anhydrase inhibitor, was investigated using liver microsomes from Sprague-Dawley rats. The liver microsomes metabolized dorzolamide to an N-deethylated form, whereas N-deethylation of dorzolamide was not detected in 10,000g supernatant from the small intestine, brain, heart, lung, kidney and spleen, or the cytosol fraction of liver. The dorzolamide N-deethylase activity was not detected without an NADPH-generating system and was inhibited by classical inhibitors for cytochrome P450, metyrapone and n-octylamine. Orphenadrine and diphenhydramine (specific inhibitors for CYP2B1/2), diethyldithiocarbamate, disulfiram and isoniazid (inhibitors for CYP2E1), troleandomycin (inhibitor for CYP3A), and testosterone inactivated dorzolamide N-deethylase activity. On the other hand, ajmalicine, a specific inhibitor for CYP2D1, did not inhibit the reaction. With phenobarbital-induced microsomes, 66%, 72%, 36%, and 53% of the 2 beta-, 6 beta-, 16 alpha-, and 16 beta-testosterone hydroxylase activities were inhibited by 5 mM dorzolamide, respectively, whereas the 2 alpha-hydroxylase activity was not inactivated. Antisera against rat CYP2B1, CYP2E1, and CYP3A2 suppressed dorzolamide N-deethylase activity by 52%, 43% and 46%, respectively, whereas only 18% and 15% of the activity were inhibited by anti-CYP1A1 and anti-CYP4A1 antibodies, respectively. Analysis of the N-deethylase reactions using Eadie-Scatchard plots showed high- and low-affinity components in rat liver microsomes. The high-affinity reaction was induced with phenobarbital and dexamethasone, but not with 3-methylcholanthrene. These results suggest that CYP2B, CYP2E1, and CYP3A subfamilies are involved in the dorzolamide N-deethylation in rat liver microsomes. PMID: 7895610 [Indexed for MEDLINE] 5. Plant Cell Rep. 1985 Aug;4(4):216-9. doi: 10.1007/BF00269293. Partial purification and characterization of a NADPH dependent tetrahydroalstonine synthase from Catharanthus roseus cell suspension cultures. Hemscheidt T(1), Zenk MH. Author information: (1)Lehrstuhl für Pharmazeutische Biologie, Universität München, Karlstrasse 29, D-8000, München 2, FRG. A new enzyme was discovered which specifically hydrogenates the iminium form of cathenamine at position 21 to yield the heteroyohimbine alkaloid tetrahydroalstonine. The enzyme was partially purified (35-fold) from Catharanthus roseus cell suspension cultures. It was shown to use exclusively NADPH as reductant, the pH optimum is at 6.6, the temperature optimum at 30°C, the half life of the soluble enzyme preparation is 26 min at 37°C, and the molecular weight is 81 000 ± 3%. Evidence is presented for the occurrence of two distinct and different cathenamine reductases, one reducing the iminium form of this central intermediate to give tetrahydroalstonine, the other one reducing cathenamine to yield ajmalicine. Tetrahydroalstonine synthase was present in cell suspension cultures of C. ovalis, C. roseus, Picralima nitida, Rhazya stricta, and Vinca herbacea. DOI: 10.1007/BF00269293 PMID: 24253886