Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. J Hazard Mater. 2024 Oct 17;480:136192. doi: 10.1016/j.jhazmat.2024.136192. 
Online ahead of print.

A comprehensive study on the digestion, absorption, and metabolization of 
tropane alkaloids in human cell models.

Marín-Sáez J(1), Lopez-Ruiz R(2), Faria MA(3), Ferreira IMPLVO(4), Garrido 
Frenich A(5).

Author information:
(1)Research Group "Analytical Chemistry of Contaminants", Department of 
Chemistry and Physics, Research Centre for Mediterranean Intensive Agrosystems 
and Agri-Food Biotechnology (CIAIMBITAL), University of Almeria, Agrifood Campus 
of International Excellence, ceiA3, E-04120 Almeria, Spain; LAQV/REQUIMTE, 
Departamento de Ciências Químicas, Laboratório de Bromatologia e Hidrologia, 
Faculdade de Farmácia, Universidade do Porto, Porto, Portugal. Electronic 
address: jms485@ual.es.
(2)Research Group "Analytical Chemistry of Contaminants", Department of 
Chemistry and Physics, Research Centre for Mediterranean Intensive Agrosystems 
and Agri-Food Biotechnology (CIAIMBITAL), University of Almeria, Agrifood Campus 
of International Excellence, ceiA3, E-04120 Almeria, Spain; LAQV/REQUIMTE, 
Departamento de Ciências Químicas, Laboratório de Bromatologia e Hidrologia, 
Faculdade de Farmácia, Universidade do Porto, Porto, Portugal. Electronic 
address: rlr468@ual.es.
(3)LAQV/REQUIMTE, Departamento de Ciências Químicas, Laboratório de Bromatologia 
e Hidrologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal. 
Electronic address: mfaria@ff.up.pt.
(4)LAQV/REQUIMTE, Departamento de Ciências Químicas, Laboratório de Bromatologia 
e Hidrologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal. 
Electronic address: isabel.ferreira@ff.up.pt.
(5)Research Group "Analytical Chemistry of Contaminants", Department of 
Chemistry and Physics, Research Centre for Mediterranean Intensive Agrosystems 
and Agri-Food Biotechnology (CIAIMBITAL), University of Almeria, Agrifood Campus 
of International Excellence, ceiA3, E-04120 Almeria, Spain. Electronic address: 
agarrido@ual.es.

Tropane alkaloids (TAs) are toxic compounds with potent anticholinergic effects. 
Herbal infusions are among the most contaminated food commodities; however, the 
fate of TAs after ingestion remains poorly understood. This study presents a 
comprehensive investigation into the absorption, and metabolism of five TAs 
(atropine, scopolamine, tropine, homatropine, and apoatropine) following the 
digestion of contaminated tea. In vitro human cell models were employed, 
including gastric (NCI-N87), intestinal (Caco-2:HT29-MTX), and hepatic (HEP-G2) 
cells. TAs were found to be highly absorbed in the intestinal epithelium, while 
gastric cells exhibited poor absorption. Metabolism was studied using a 
custom-made database, revealing that it occurs predominantly in intestinal 
cells, involving hydroxylation and methylation reactions. Cell metabolomics was 
conducted using annotation, fragment simulation, and statistical software 
platforms. Significant statistical differences were observed for 40 tentatively 
identified compounds. MetaboAnalyst 5.0 was employed to discern the most 
disturbed metabolic pathways, with amoniacids biosynthesis pathways and TCA 
cycles being the most affected. These pathways are involved in responses to 
cellular metabolic stress, neurotransmitter production, cellular energy 
generation, and the regulation of oxidative stress response. The findings of 
this study enhance our understanding of the fate of TAs after ingestion, their 
metabolization and their effects at the cellular level.

Copyright © 2024 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.jhazmat.2024.136192
PMID: 39427354

Conflict of interest statement: Declaration of Competing Interest The authors 
declare that they have no known competing financial interests or personal 
relationships that could have appeared to influence the work reported in this 
paper.


2. Front Pharmacol. 2024 Jun 24;15:1405461. doi: 10.3389/fphar.2024.1405461. 
eCollection 2024.

Tropine exacerbates the ventilatory depressant actions of fentanyl in 
freely-moving rats.

Getsy PM(1), May WJ(2), Young AP(2), Baby SM(3), Coffee GA(1), Bates JN(4), 
Hsieh YH(5), Lewis SJ(1)(6)(7).

Author information:
(1)Department of Pediatrics, Case Western Reserve University, Cleveland, OH, 
United States.
(2)Department of Pediatrics, University of Virginia, Charlottesville, VA, United 
States.
(3)Galleon Pharmaceuticals, Inc., Horsham, PA, United States.
(4)Department of Anesthesiology, University of Iowa Hospitals and Clinics Iowa, 
Iowa City, IA, United States.
(5)Division of Pulmonary, Critical Care and Sleep Medicine, University Hospitals 
Case Medical Center, Case Western Reserve University, Cleveland, OH, United 
States.
(6)Department of Pharmacology, Case Western Reserve University, Cleveland, OH, 
United States.
(7)Functional Electrical Stimulation Center, Case Western Reserve University, 
Cleveland, OH, United States.

Our lab is investigating the efficacy profiles of tropine analogs against 
opioid-induced respiratory depression. The companion manuscript reports that the 
cell-permeant tropeine, tropine ester (Ibutropin), produces a rapid and 
sustained reversal of the deleterious actions of fentanyl on breathing, 
alveolar-arterial (A-a) gradient (i.e., index of alveolar gas exchange), and 
arterial blood-gas (ABG) chemistry in freely-moving male Sprague Dawley rats, 
while not compromising fentanyl analgesia. We report here that in contrast to 
Ibutropin, the injection of the parent molecule, tropine (200 μmol/kg, IV), 
worsens the adverse actions of fentanyl (75 μg/kg, IV) on ventilatory parameters 
(e.g., frequency of breathing, tidal volume, minute ventilation, peak 
inspiratory and expiratory flows, and inspiratory and expiratory drives), A-a 
gradient, ABG chemistry (e.g., pH, pCO2, pO2, and sO2), and sedation (i.e., the 
righting reflex), while not affecting fentanyl antinociception (i.e., the 
tail-flick latency) in freely-moving male Sprague Dawley rats. These data 
suggest that tropine augments opioid receptor-induced signaling events that 
mediate the actions of fentanyl on breathing and alveolar gas exchange. The 
opposite effects of Ibutropin and tropine may result from the ability of 
Ibutropin to readily enter peripheral and central cells. Of direct relevance is 
that tropine, resulting from the hydrolysis of Ibutropin, would combat the 
Ibutropin-induced reversal of the adverse effects of fentanyl. Because numerous 
drug classes, such as cocaine, atropine, and neuromuscular blocking drugs 
contain a tropine moiety, it is possible that their hydrolysis to tropine has 
unexpected/unintended consequences. Indeed, others have found that tropine 
exerts the same behavioral profile as cocaine upon central administration. 
Together, these data add valuable information about the pharmacological 
properties of tropine.

Copyright © 2024 Getsy, May, Young, Baby, Coffee, Bates, Hsieh and Lewis.

DOI: 10.3389/fphar.2024.1405461
PMCID: PMC11228531
PMID: 38978984

Conflict of interest statement: Author SB was employed by Galleon 
Pharmaceuticals, Inc. The remaining authors declare that the research was 
conducted in the absence of any commercial or financial relationships that could 
be construed as a potential conflict of interest. The author(s) declared that 
they were an editorial board member of Frontiers at the time of submission. This 
had no impact on the peer review process and the final decision.


3. Anal Bioanal Chem. 2024 Jul 3. doi: 10.1007/s00216-024-05401-x. Online ahead
of  print.

Colorimetric enzymatic rapid test for the determination of atropine in baby food 
using a smartphone.

Domínguez M(1)(2), Moraru D(1), Lasso S(1), Sanz-Vicente I(1)(2), de Marcos 
S(3)(4), Galbán J(1)(2).

Author information:
(1)Analytical Chemistry Department, University of Zaragoza, 50009, Saragossa, 
Spain.
(2)Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de 
Zaragoza, 50009, Saragossa, Spain.
(3)Analytical Chemistry Department, University of Zaragoza, 50009, Saragossa, 
Spain. smarcos@unizar.es.
(4)Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de 
Zaragoza, 50009, Saragossa, Spain. smarcos@unizar.es.

A method for the enzymatic determination of atropine has been developed, which 
is based on a sequence of reactions involving (1) the hydrolysis of atropine to 
give tropine; (2) the enzymatic oxidation of tropine with NAD (catalysed by 
tropinone reductase); and (3) an indicator reaction, in which the NADH 
previously formed reduces the dye iodonitrotetrazolium chloride (INT) to a 
reddish species, the reaction catalysed by diaphorase. The method was first 
developed in solution (linear response range from 2.4 × 10-6 M to 1.0 × 10-4 M). 
It was then implemented in cellulose platforms to develop a rapid test where the 
determination is made by measuring the RGB coordinates of the platforms using a 
smartphone-based device. The device is based on the integrating sphere concept 
and contains a light source to avoid external illumination effects. The 
smartphone is controlled by an app that allows a calibration line to be 
generated and the atropine concentration to be quantified; moreover, since the 
app normalizes the CCD response of the smartphone, the results and calibrations 
obtained with different smartphones are similar and can be shared. Using the G 
coordinate, the results were shown to have a linear response with the 
concentration of atropine ranging from 1.2 × 10-5 M to 3.0 × 10-4 M with an RSD 
of 1.4% (n = 5). The method has been applied to the determination of atropine in 
baby food and buckwheat samples with good results.

© 2024. The Author(s).

DOI: 10.1007/s00216-024-05401-x
PMID: 38960939


4. RSC Adv. 2024 Apr 25;14(19):13452-13462. doi: 10.1039/d3ra08960f. eCollection 
2024 Apr 22.

An efficient catalysis for the synthesis of pyrimido[1,2-a]benzimidazoles and 
1-(benzothiazolylamino)methyl-2-naphthols using ZnO@SO(3)H@Tropine.

Rahimizadeh F(1), Mazloumi M(1), Shirini F(1).

Author information:
(1)Department of Chemistry, College of Science, University of Guilan Rasht 
41335-19141 Iran shirini@guilan.ac.ir fshirini@gmail.com +98 131 3233262 +98 131 
3233262.

In this research and in the line of our researches on the use of nano-substrates 
modified with ionic liquid in organic reactions, an efficient and green method 
for the one-pot three-component synthesis of pyrimido[1,2-a]benzimidazole and 
1-(benzothiazolylamino)methyl-2-naphthol derivatives is reported using a new 
nanoporous catalyst formulated as ZnO@SO3H@Tropine. Further analysis of the 
catalyst for its characterization has been performed using thermal gravimetric 
analysis (TGA), field emission scanning electron microscopy (FESEM), X-ray 
diffraction (XRD), energy dispersive spectrometer (EDS) and Fourier-transform 
infrared spectroscopy (FT-IR). The present approach creates a variety of 
biologically active heterocyclic compounds with excellent yields and short 
reaction times. Among the other advantages of the current method are: ease of 
operation, clean reaction profiles and ease of separation. Also, this catalyst 
can be reused five times without loss of its catalytic activity.

This journal is © The Royal Society of Chemistry.

DOI: 10.1039/d3ra08960f
PMCID: PMC11043802
PMID: 38665495

Conflict of interest statement: There are no conflicts to declare.


5. Chem Biodivers. 2024 Jun;21(6):e202301477. doi: 10.1002/cbdv.202301477. Epub 
2024 May 9.

A Review on the Chemical Properties, Plant Sources, Anti-shock Effects, 
Pharmacokinetics, Toxicity, and Clinical Applications of Anisodamine.

Xia Q(1), Pingcuo R(2), Yang C(3)(4), Xiong W(4), Peng X(3)(4), Xia J(4), Wang 
W(3)(4), Hai M(1).

Author information:
(1)College of Agronomy and Biotechnology, Yunnan Agricultural University, 
Kunming, 650201, China.
(2)Limei Tibetan Medicine Hospital, Liwuqi, 855600, China.
(3)School of Pharmacy, Chongqing Three Gorges Medical Colleges, Chongqing, 
404120, China.
(4)Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal 
Materials in Three Gorges Reservoir Area, Chongqing, 404120, China.

Alkaloids are natural products that occur widely in many herbal plants. 
Anisodamine, widely present in the Solanaceae family, is an alkaloid extracted 
from the roots of the Anisodus tanguticus Maxim. It is an antagonist to 
M-choline receptors and exhibits diverse pharmacological effects, such as 
cholinolytic effect, calcium antagonist effect, anti-oxygenation effect. 
Anisodamine, a prominent constituent of the tropine alkaloid family, exhibits a 
range of pharmacological effects akin to those of atropine and scopolamine. 
owing to its low toxicity and moderate efficacy in clinical to wide 
applications, especially for varieties of shock treatment. However, there 
remains a dearth of research regarding the in vivo pharmacokinetics, mechanism 
of action, and toxicity of anisodamine. Consequently, this paper provides a 
comprehensive review of the anti-shock effects, toxicity, and pharmacokinetic 
characteristics of anisodamine to increase the understanding of its medicinal 
value, and provide reference and inspiration for the clinical application and 
further in-depth research of anisodamine.

© 2024 Wiley-VHCA AG, Zurich, Switzerland.

DOI: 10.1002/cbdv.202301477
PMID: 38415906 [Indexed for MEDLINE]