-
Toxins Apr 2022Cocaine is one of the most consumed stimulants throughout the world, as official sources report. It is a naturally occurring sympathomimetic tropane alkaloid derived... (Review)
Review
Cocaine is one of the most consumed stimulants throughout the world, as official sources report. It is a naturally occurring sympathomimetic tropane alkaloid derived from the leaves of , which has been used by South American locals for millennia. Cocaine can usually be found in two forms, cocaine hydrochloride, a white powder, or 'crack' cocaine, the free base. While the first is commonly administered by insufflation ('snorting') or intravenously, the second is adapted for inhalation (smoking). Cocaine can exert local anaesthetic action by inhibiting voltage-gated sodium channels, thus halting electrical impulse propagation; cocaine also impacts neurotransmission by hindering monoamine reuptake, particularly dopamine, from the synaptic cleft. The excess of available dopamine for postsynaptic activation mediates the pleasurable effects reported by users and contributes to the addictive potential and toxic effects of the drug. Cocaine is metabolised (mostly hepatically) into two main metabolites, ecgonine methyl ester and benzoylecgonine. Other metabolites include, for example, norcocaine and cocaethylene, both displaying pharmacological action, and the last one constituting a biomarker for co-consumption of cocaine with alcohol. This review provides a brief overview of cocaine's prevalence and patterns of use, its physical-chemical properties and methods for analysis, pharmacokinetics, pharmacodynamics, and multi-level toxicity.
Topics: Cocaine; Dopamine; Ethanol
PubMed: 35448887
DOI: 10.3390/toxins14040278 -
ACS Chemical Neuroscience Oct 2018In this Review, we consider the story of cocaine from its humble origins in South America to its status as one of the most abused substances in 21st century society. The... (Review)
Review
In this Review, we consider the story of cocaine from its humble origins in South America to its status as one of the most abused substances in 21st century society. The synthesis and biosynthesis of cocaine are discussed, as well as its pharmacokinetics, metabolism, pharmacology, and importance in modern neuroscience and molecular imaging.
Topics: Cocaine; Crack Cocaine; Dopamine Uptake Inhibitors; History, 19th Century; History, 20th Century; History, 21st Century; Humans
PubMed: 29630337
DOI: 10.1021/acschemneuro.8b00117 -
Anais Da Academia Brasileira de Ciencias 2015This study assessed the occurrence and distribution of tropane alkaloids and calystegines in genera of the family Solanaceae to identify patterns of distribution and... (Review)
Review
This study assessed the occurrence and distribution of tropane alkaloids and calystegines in genera of the family Solanaceae to identify patterns of distribution and make evolutionary inferences. A database of tropane alkaloids and calystegines occurrences was constructed from the results of a search of scientific websites and a hand search of periodicals. The terms "Solanaceae", "tropane alkaloids", and "calystegines" were used as index terms for a full-text article search unrestricted by date of publications. The number of occurrence and chemical diversity indices were calculated and cluster analysis and principal components analysis were performed. Overall, 996 occurrences were reported, 879 of tropane alkaloids (88.3%) and 117 of calystegines (11.7%). The calystegines were significantly more relevant than tropane alkaloids for characterization of distinct groups of genera on both analyses performed here. This corroborates the trend toward a chemical dichotomy observed on database analysis and somewhat reinforces the correlation between geographic distribution and occurrence of secondary metabolites, as the presence of calystegines alone (without tropane alkaloids) was only reported in genera that have South America as their center of diversity.
Topics: Biomarkers; Gas Chromatography-Mass Spectrometry; Solanaceae; Solanaceous Alkaloids; Tropanes
PubMed: 26536852
DOI: 10.1590/0001-3765201520140231 -
Molecules (Basel, Switzerland) Nov 2016The tropane and granatane alkaloids belong to the larger pyrroline and piperidine classes of plant alkaloids, respectively. Their core structures share common moieties... (Review)
Review
The tropane and granatane alkaloids belong to the larger pyrroline and piperidine classes of plant alkaloids, respectively. Their core structures share common moieties and their scattered distribution among angiosperms suggest that their biosynthesis may share common ancestry in some orders, while they may be independently derived in others. Tropane and granatane alkaloid diversity arises from the myriad modifications occurring to their core ring structures. Throughout much of human history, humans have cultivated tropane- and granatane-producing plants for their medicinal properties. This manuscript will discuss the diversity of their biological and ecological roles as well as what is known about the structural genes and enzymes responsible for their biosynthesis. In addition, modern approaches to producing some pharmaceutically important tropanes via metabolic engineering endeavors are discussed.
Topics: Alkaloids; Biosynthetic Pathways; Metabolic Engineering; Plant Extracts; Secondary Metabolism; Tropanes
PubMed: 27845728
DOI: 10.3390/molecules21111510 -
Molecules (Basel, Switzerland) Feb 2019Tropane alkaloids (TA) are valuable secondary plant metabolites which are mostly found in high concentrations in the Solanaceae and Erythroxylaceae families. The TAs,... (Review)
Review
Tropane alkaloids (TA) are valuable secondary plant metabolites which are mostly found in high concentrations in the Solanaceae and Erythroxylaceae families. The TAs, which are characterized by their unique bicyclic tropane ring system, can be divided into three major groups: hyoscyamine and scopolamine, cocaine and calystegines. Although all TAs have the same basic structure, they differ immensely in their biological, chemical and pharmacological properties. Scopolamine, also known as hyoscine, has the largest legitimate market as a pharmacological agent due to its treatment of nausea, vomiting, motion sickness, as well as smooth muscle spasms while cocaine is the 2nd most frequently consumed illicit drug globally. This review provides a comprehensive overview of TAs, highlighting their structural diversity, use in pharmaceutical therapy from both historical and modern perspectives, natural biosynthesis and emerging production possibilities using tissue culture and microbial biosynthesis of these compounds.
Topics: Alkaloids; Erythroxylaceae; Gene Expression Regulation, Plant; Humans; Molecular Structure; Plant Extracts; Secondary Metabolism; Solanaceae; Tropanes
PubMed: 30813289
DOI: 10.3390/molecules24040796 -
Toxins Sep 2017Tropane alkaloids occur mainly in plants. In the present review, the main objective is to describe the worldwide occurrence and investigations of anticholinergic... (Review)
Review
Tropane alkaloids occur mainly in plants. In the present review, the main objective is to describe the worldwide occurrence and investigations of anticholinergic poisoning due to the contamination of herbal teas and herbs by tropane alkaloids. Tropane alkaloid poisoning can occur after consumption of any medicinal plant if plants or plant parts are present as contaminants. Globally, almost all reports in 1978-2014 involve herbal teas and one of the prescribed herbs in composite formulae. Contamination most likely occurs during harvest or processing. As for prescribed herbs, on-site inspection is necessary to exclude cross-contamination and accidental mix-up at the retail level. The diagnosis is confirmed by screening for the presence of species and tropane alkaloids. Herbal teas and herbs contaminated by tropane alkaloids can pose a serious health hazard because these relatively heat-stable alkaloids may exist in large quantities. The WHO repeatedly emphasises the importance of good agricultural and collection practices for medicinal plants. DNA barcoding is increasingly used to exclude the presence of contaminants (particularly toxic species) and product substitution. All suspected cases should be reported to health authorities so that investigations along the supply chain and early intervention measures to protect the public can be initiated.
Topics: Alkaloids; Drug Contamination; Humans; Plants, Medicinal; Tropanes
PubMed: 28914776
DOI: 10.3390/toxins9090284 -
Respiratory Care May 2020Relevant publications related to medicinal and toxic aerosols are discussed in this review. Treatment of COPD includes a combination of long-acting bronchodilators and... (Review)
Review
Relevant publications related to medicinal and toxic aerosols are discussed in this review. Treatment of COPD includes a combination of long-acting bronchodilators and long-acting muscarinic antagonists. A combination of aclidinium bromide and formoterol fumarate was approved in the United States. The combination was superior to its components alone, as well as tiotropium and a salmeterol-fluticasone combination. Increased risk of an asthma exacerbation was reported in children exposed to electronic nicotine delivery systems. A smart inhaler capable of recording inspiratory flow was approved in the United States. The use of as-needed budesonide-formoterol was reported to be superior to scheduled budesonide and as-needed terbutaline for the treatment of adults with mild-to-moderate asthma. A survey among teens with asthma and their caregivers revealed a disagreement in the number of inhaled controller medications the teen was taking. Treatment with inhaled hypertonic saline resulted in a decreased lung clearance index in infants and preschool children with cystic fibrosis. Surgical masks were well tolerated and significantly decreased the burden of aerosolized bacteria generated by coughing in adults with cystic fibrosis. Inhaled liposomal amikacin in addition to guideline-based therapy was reported to be superior to guideline-based therapy alone in achieving negative sputum cultures in adult subjects with complex pulmonary disease. During 2019, lung injury associated to e-cigarette or vaping was reported, including 60 casualties.
Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Electronic Nicotine Delivery Systems; Formoterol Fumarate; Humans; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Tiotropium Bromide; Tropanes
PubMed: 32345761
DOI: 10.4187/respcare.07738 -
Respirology (Carlton, Vic.) Oct 2017
Topics: Administration, Inhalation; Bronchodilator Agents; Humans; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide
PubMed: 28712128
DOI: 10.1111/resp.13126 -
Proceedings of the National Academy of... Apr 2023The tropane alkaloids (TAs) cocaine and hyoscyamine have been used medicinally for thousands of years. To understand the evolutionary origins and trajectories of serial...
The tropane alkaloids (TAs) cocaine and hyoscyamine have been used medicinally for thousands of years. To understand the evolutionary origins and trajectories of serial biosynthetic enzymes of TAs and especially the characteristic tropane skeletons, we generated the chromosome-level genome assemblies of cocaine-producing (Erythroxylaceae, rosids clade) and hyoscyamine-producing (Solanaceae, asterids clade). Comparative genomic and phylogenetic analysis suggested that the lack of spermidine synthase/-methyltransferase (SPMT1) in ancestral asterids species contributed to the divergence of polyamine (spermidine or putrescine) methylation in cocaine and hyoscyamine biosynthesis. Molecular docking analysis and key site mutation experiments suggested that ecgonone synthases CYP81AN15 and CYP82M3 adopt different active-site architectures to biosynthesize the same product ecgonone from the same substrate in Erythroxylaceae and Solanaceae. Further synteny analysis showed different evolutionary origins and trajectories of CYP81AN15 and CYP82M3, particularly the emergence of through the neofunctionalization of ancient tandem duplication genes. The combination of structural biology and comparative genomic analysis revealed that ecgonone methyltransferase, which is responsible for the biosynthesis of characteristic 2-substituted carboxymethyl group in cocaine, evolved from the tandem copies of salicylic acid methyltransferase by the mutations of critical E216 and S153 residues. Overall, we provided strong evidence for the independent origins of serial TA biosynthetic enzymes on the genomic and structural level, underlying the chemotypic convergence of TAs in phylogenetically distant species.
Topics: Hyoscyamine; Phylogeny; Molecular Docking Simulation; Tropanes; Solanaceae; Genomics; Cocaine; Methyltransferases
PubMed: 37068250
DOI: 10.1073/pnas.2302448120 -
Toxins Apr 2024Anatoxin-a (ATX-a) is a potent neurotoxin produced by several species of cyanobacteria whose exposure can have direct consequences, including neurological disorders and... (Review)
Review
Anatoxin-a (ATX-a) is a potent neurotoxin produced by several species of cyanobacteria whose exposure can have direct consequences, including neurological disorders and death. The increasing prevalence of harmful cyanobacterial blooms makes the detection and reliable assessment of ATX-a levels essential to prevent the risk associated with public health. Therefore, the aim of this review is to compile the analytical methods developed to date for the detection and quantification of ATX-a levels alone and in mixtures with other cyanotoxins and their suitability. A classification of the analytical methods available is fundamental to make an appropriate choice according to the type of sample, the equipment available, and the required sensitivity and specificity for each specific purpose. The most widely used detection technique for the quantification of this toxin is liquid chromatography-tandem mass spectrometry (LC-MS/MS). The analytical methods reviewed herein focus mainly on water and cyanobacterial samples, so the need for validated analytical methods in more complex matrices (vegetables and fish) for the determination of ATX-a to assess dietary exposure to this toxin is evidenced. There is currently a trend towards the validation of multitoxin methods as opposed to single-ATX-a determination methods, which corresponds to the real situation of cyanotoxins' confluence in nature.
Topics: Cyanobacteria Toxins; Tropanes; Tandem Mass Spectrometry; Chromatography, Liquid; Cyanobacteria; Animals; Humans; Food Contamination
PubMed: 38668623
DOI: 10.3390/toxins16040198