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e Effect of the mobile phase of acetonitrileewater on the retention of six Salvia species spiked with 10 mg/mL salvinorin A. (A) Acetonitrileewater (45:55, v/v) at a flow rate of 1.0 mL/min; (B) acetonitrileewater (40:60, v/v) at a flow rate of 1.0 mL/min; (C) acetonitrileewater (35:65, v/v) at a flow rate of 1.0 mL/min; (D) acetonitrileewater (35:65, v/v) at a flow rate of 1.5 mL/min.
Source publication
In recent years, recreational use of Salvia divinorum (Lamiaceae), a herbal drug that contains a hallucinogenic ingredient, salvinorin A, has become a new phenomenon among young drug users. In Taiwan, as in many other countries, dry leaves of S. divinorum and its related concentrated extract products are available via the Internet. Besides S. divin...
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Context 1
... mobile phase composition, modified by Gruber et al [22], consisted of a mixed extraction of six endemic Salvia species in Taiwan spiked with 10 mg/mL salvinorin A. Fig. 2A and B showed that in the initial mobile phase of acetonitrileewater (45:55, v/v) with a flow rate of 1.0 mL/min and the modification of the ace- tonitrileewater (40:60, v/v) with a flow rate of 1.0 mL/min, the salvinorin A peak was interfered with by the endogenous components of the crude extraction of the mixed six endemic Salvia species. In the modified mobile phase of acetonitrilee- water (35:65, v/v) at a flow rate of 1.0 mL/min, the salvinorin A peak was not eluted within 55 minutes (Fig. 2C). The modified mobile phase of acetonitrileewater (35:65, v/v) with a flow rate of 1.5 mL/min under isocratic elution had a better separation efficiency in the mixed extraction, leading to salvinorin A being eluted at approximately 48.85 minutes (Fig. 2D). Theoretically, a shorter retention time could be achieved with shorter analytical columns, such as 150 Â 4.6 Â 5 mm. In this study, the separation condition was not further approached because the analytical evaluation of salvinorin A content in Salvia species for the administrative purpose had been ...
Context 2
... mobile phase composition, modified by Gruber et al [22], consisted of a mixed extraction of six endemic Salvia species in Taiwan spiked with 10 mg/mL salvinorin A. Fig. 2A and B showed that in the initial mobile phase of acetonitrileewater (45:55, v/v) with a flow rate of 1.0 mL/min and the modification of the ace- tonitrileewater (40:60, v/v) with a flow rate of 1.0 mL/min, the salvinorin A peak was interfered with by the endogenous components of the crude extraction of the mixed six endemic Salvia species. In the modified mobile phase of acetonitrilee- water (35:65, v/v) at a flow rate of 1.0 mL/min, the salvinorin A peak was not eluted within 55 minutes (Fig. 2C). The modified mobile phase of acetonitrileewater (35:65, v/v) with a flow rate of 1.5 mL/min under isocratic elution had a better separation efficiency in the mixed extraction, leading to salvinorin A being eluted at approximately 48.85 minutes (Fig. 2D). Theoretically, a shorter retention time could be achieved with shorter analytical columns, such as 150 Â 4.6 Â 5 mm. In this study, the separation condition was not further approached because the analytical evaluation of salvinorin A content in Salvia species for the administrative purpose had been ...
Context 3
... mobile phase composition, modified by Gruber et al [22], consisted of a mixed extraction of six endemic Salvia species in Taiwan spiked with 10 mg/mL salvinorin A. Fig. 2A and B showed that in the initial mobile phase of acetonitrileewater (45:55, v/v) with a flow rate of 1.0 mL/min and the modification of the ace- tonitrileewater (40:60, v/v) with a flow rate of 1.0 mL/min, the salvinorin A peak was interfered with by the endogenous components of the crude extraction of the mixed six endemic Salvia species. In the modified mobile phase of acetonitrilee- water (35:65, v/v) at a flow rate of 1.0 mL/min, the salvinorin A peak was not eluted within 55 minutes (Fig. 2C). The modified mobile phase of acetonitrileewater (35:65, v/v) with a flow rate of 1.5 mL/min under isocratic elution had a better separation efficiency in the mixed extraction, leading to salvinorin A being eluted at approximately 48.85 minutes (Fig. 2D). Theoretically, a shorter retention time could be achieved with shorter analytical columns, such as 150 Â 4.6 Â 5 mm. In this study, the separation condition was not further approached because the analytical evaluation of salvinorin A content in Salvia species for the administrative purpose had been ...
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In recent years, national laboratories have identified several plant-derived materials as concerns to public health because of their psychoactive effects, potential for abuse, and the lack of federal regulation of their use. One of these is Salvia divinorum (aka Salvia), which has received focused attention due to its increasing recreational use an...
Salvia divinorum Epling and Játiva is a perennial mint from the Lamiaceae family, endemic to Mexico, predominantly from the state of Oaxaca. Due to its psychoactive properties, S. divinorum had been used for centuries by Mazatecans for divinatory, religious, and medicinal purposes. In recent years, its use for recreational purposes, especially amon...
Citations
... In Mexico research on legal drugs determined the salvinorin A range from 8.32 to 56.52 mg · 1 g -1 dried leaf in the species mentioned. Investigators have established that 200-500 μg of salvinorin A induces strong hallucinogenic effects lasting for 20-30 min [32][33][34][35] . Salvinorins A and B represent diterpenes of neo clerodane. ...
Coleus scutellarioides (L.) Benth. is a popular species in the world, known for its characteristic magnificent colourful leaves. The study has revealed that the contents of rosmarinic acid and caffeic acid are significantly higher in the plant tissues cultivated in vivo than when under in vitro conditions. The performed qualitative and quantitative analyses confirmed the presence (whose averaged content) of salvinorin A (6.65 µg/1 g of fresh plant) and salvinorin B (50.46 µg/1 g of fresh plant) in tissues of Coleus scutellarioides (L.) Benth. of ‘Electric lime’ variety. The greatest quantities of these compounds were recorded for plants cultivated in vitro on the MS medium enriched with NAA (naphthyl-1-acetic acid) at a concentration of 0.5 mg∙ dm–3. The research detected differences in the amounts of compounds between plants grown in vivo and those cultivated in vitro. Addition of plant growth regulators into the breeding medium under in vitro conditions was found affecting the amounts of compounds in plant tissues.
... The recreational use of S. divinorum, however, has led to restrictions in 32 US states and 20 countries, limiting access to plant-sourced materials for broad-development. 61 The synthesis reported here quickly enters the chemical space of salvinorin A and accesses new analogs at C11 and C12 that exceed the stability, potency, selectivity and G protein bias of the natural product itself. Whereas an early salvinorin analog, herkinorin, exhibited the first example of MOR-selective G protein bias, 62 corresponding KORselective biased agonists have proven harder to develop; the prevalence of functional bias in Figure 4C further discovery. ...
The salvinorins serve as templates for next generation analgesics, antipruritics and dissociative hallucinogens via selective and potent agonism of the kappa-opioid receptor (KOR). In contrast to most opioids, the salvinorins lack basic amines and bind with high affinity and selectivity via complex polyoxygenated scaffolds that have frustrated deep-seated modification by synthesis. Here we describe a short asymmetric synthesis that relies on a sterically-confined organocatalyst to dissociate acidity from reactivity and effect Robinson annulation of an unactivated nucleophile / unstable electrophile pair. Combined with a cobalt-catalyzed polarized diene-alkyne cycloaddition, the route allows divergent access to a focused library of salvinorins. We appraise the synthesis by its generation of multiple analogs that exceed the potency, selectivity, stability and functional bias of salvinorin A itself.
... The concentrations of salvinorin A in raw Salvia leaves reported in previous studies range from 0.89 to 7.8 mg/ g. [20][21][22]41,43 Salvia stems have also been investigated and were found to contain less than 0.63 mg/g of salvinorin A. 21 Significant effort has been dedicated to quantifying salvinorin A in enhanced Salvia leaf products. Concentrations or concentration ranges published to date and organized according to the potency listed on the product labels are as follows: 4. The study presented here features raw Salvia leaves and multiple enhanced leaf products of various potency levels. ...
... These salvinorin A results, which are shown in bar chart form in Figure 6, are fairly similar to those appearing in the reports published to date. [20][21][22][23]43,44 In particular, the salvinorin A concentration in the raw Salvia leaves and Salvia 5×, 10×, 15×, and 20× products all fall within the ranges reported in the literature. Nevertheless, there were some deviations between the experimentally determined and literature values of salvinorin A, for the Salvia 40× and Salvia 60× products, in that they fell below previously reported values or ranges. ...
In recent years, national laboratories have identified several plant-derived materials as concerns to public health because of their psychoactive effects, potential for abuse, and the lack of federal regulation of their use. One of these is Salvia divinorum (aka Salvia), which has received focused attention due to its increasing recreational use and the ease by which it can be acquired. Traditional chromatographic approaches for the detection of the major psychoactive component of Salvia (i.e., salvinorin A) typically require time-consuming sample pretreatment prior to identifying the presence of salvinorin A in plant material unknowns. In this study, direct analysis in real time–high-resolution mass spectrometry (DART-HRMS) was used to rapidly screen for Salvia plant material. This approach facilitated the analysis of bulk material in its native form, thereby bypassing sample pretreatment steps. In addition, a validated DART-HRMS method was developed for the quantification of salvinorin A in commercial Salvia products (e.g., raw plant materials, enhanced leaf extracts). In this regard, cholesterol was found to be a suitable internal standard. The average salvinorin A content in raw Salvia leaves was determined to be 1.54 mg/g, while the salvinorin A quantified in enhanced Salvia leaf extracts was between 13.0 and 53.2 mg/g.
... In the following years, countries like Spain, Germany, Denmark, Belgium, Sweden, Poland, Italy, France, and Croatia placed S. divinorum, salvinorin A, or both on their lists of controlled substances, prohibiting possession and/or sale [66][67][68]. Notwithstanding, in Norway, Iceland, Finland, and Estonia, this plant can be legally used for medicinal purposes, including in the treatment of cocaine dependence [69,70]. In Portugal, Decree n o 54/2013, 17 of April prohibited the production, distribution, sale, and possession of S. divinorum, salvinorin A and salvinorin B [71]. ...
Salvia divinorum Epling and Játiva is a perennial mint from the Lamiaceae family, endemic to Mexico, predominantly from the state of Oaxaca. Due to its psychoactive properties, S. divinorum had been used for centuries by Mazatecans for divinatory, religious, and medicinal purposes. In recent years, its use for recreational purposes, especially among adolescents and young adults, has progressively increased. The main bioactive compound underlying the hallucinogenic effects, salvinorin A, is a non-nitrogenous diterpenoid with high affinity and selectivity for the k-opioid receptor. The aim of this work is to comprehensively review and discuss the toxicokinetics and toxicodynamics of S. divinorum and salvinorin A, highlighting their psychological, physiological, and toxic effects. Potential therapeutic applications and forensic aspects are also covered in this review. The leaves of S. divinorum can be chewed, drunk as an infusion, smoked, or vaporised. Absorption of salvinorin A occurs through the oral mucosa or the respiratory tract, being rapidly broken down in the gastrointestinal system to its major inactive metabolite, salvinorin B, when swallowed. Salvinorin A is rapidly distributed, with accumulation in the brain, and quickly eliminated. Its pharmacokinetic parameters parallel well with the short-lived psychoactive and physiological effects. No reports on toxicity or serious adverse outcomes were found. A variety of therapeutic applications have been proposed for S. divinorum which includes the treatment of chronic pain, gastrointestinal and mood disorders, neurological diseases, and treatment of drug dependence. Notwithstanding, there is still limited knowledge regarding the pharmacology and toxicology features of S. divinorum and salvinorin A, and this is needed due to its widespread use. Additionally, the clinical acceptance of salvinorin A has been hampered, especially due to the psychotropic side effects and misuse, turning the scientific community to the development of analogues with better pharmacological profiles.
... According to the 2019 World Drug Report, as of December 2018, the United Nations Office on Drugs and Crime (UNODC) identified a total of 892 NPS; the number was more than triple than the 273 substances controlled under the 1961 and 1971 conventions [3]. These NPS, classified by the UNODC into nine categories, including synthetic cannabinoids, synthetic cathinones, ketamine and PCP-type substances, phenethylamines, piperazines, tryptamines, aminoindanes, plant-based substances, and others [4], are predominantly derivatives or analogs of existing controlled substances [5,6]. Because of their elusiveness from the United Nations Drug Conventions and uncertain toxicological profiles, the NPS may pose a potential threat to public health and social security [7,8]. ...
... Some other NPS categories, such as synthetic cannabinoids (e.g. JWH-250, JWH-018), phenethylamines, and plant-based substances [Kratom (Mitragyna speciosa) and Salvia (Salvia divinorum)] have also been reported [1,5,8,11,13,18,20]. Apparently, abused NPS have been diversified in both categories and items. ...
Purpose of review:
Abuse of new psychoactive substances (NPS) has been a new global concern. So far, there has been no international consensus on legislative control of NPS. Scrutiny of Taiwan's illegal drug use history reveals that legislation and policy play an important role in tackling the drug issues.
Recent findings:
Since the early 2000s, use of club drugs (mostly NPS) has become popular in local rave parties and dance clubs in Taiwan. Some NPS, such as ketamine, synthetic cathinones, and para-methoxymethamphetamine, have posed a risk to public health and a challenge to drug policy.
Summary:
The illegal drug use history in Taiwan was firstly briefly reviewed, and the recent NPS use situation was depicted. Heroin and methamphetamine have been the most predominant drugs, but NPS such as ketamine and synthetic cathinones have become a new issue. The toxicological profiles of commonly abused NPS in Taiwan, although limited, were discussed. By comparison of the legislative mechanism for NPS control between Taiwan, South Korea, and Japan, it was found that timely and flexible legislative mechanism(s) is essential for early identification, surveillance, and comprehensive evaluation. In addition, researches on NPS epidemiology and toxicology are needed to firm up evidence-based strategies for effective prevention, treatment, and harm reduction measures.
... Thin layer chromatography using desorption electrospray ionization mass spectrometry (TLC-DESI-MS) [220], thin layer chromatography teamed with gas chromatography/mass spectrometry (TLC-GS/ MS) [221,222] and using HPLC coupled with UV detector [223][224][225][226], using NMR [227] have been used to detect SA in S. divinorum leaves and herbal products. ...
New psychoactive substances (NPS) can be divided into two main groups: synthetic molecules and active principles of natural origin. With respect to this latter group, a wide range of alkaloids contained in plants, mainly from Asia and South America, can be included in the class of NPS of natural origin. The majority NPS of natural origin presents stimulant and/or hallucinogenic effects (e.g. Catha edulis and Ayahuasca, respectively) while few of them show sedative and relaxing properties (e.g. kratom). Few information is available in relation to the analytical identification of psychoactive principles contained in the plant material. Moreover, to our knowledge, scarce data are present in literature, about the characterization and quantification of the parent drug in biological matrices from intoxication and fatality cases. In addition, the metabolism of natural active principles has not been yet fully investigated for most of the psychoactive substances from plant material. Consequently, their identification is not frequently performed and produced metabolites are often unknown. To fill this gap, we reviewed the currently available analytical methodologies for the identification and quantification of NPS of natural origin in plant material and, whenever possible, in conventional and non-conventional biological matrices of intoxicated and dead subjects. The psychoactive principles contained in the following plants were investigated: Areca catechu, Argyreia nervosa, Ayahuasca, Catha edulis, Ipomoea violacea, Mandragora officinarum, Mitragyna speciosa, Pausinystalia yohimbe, Piper methisticum, Psilocybe, Rivea corymbosa, Salvia divinorum, Sceletium tortuosum, Lactuca virosa. From the results obtained, it can be evidenced that although several analytical methods for the simultaneous quantification of different molecules from the same plants have been developed and validated, a comprehensive method to detect active compounds from different natural specimens both in biological and non-biological matrices is still lacking.
... Among the species having adverse effects, Salvia divinorum (Epling and Javita), a member of the Lamiaceae (Labiatae) family, is endemic to the northern Sierra Mazateca mountain of Mexico. It was used by Mazatec Indians in spiritual rituals to have hallucinatory effects (Bertea et al., 2005;Bertea et al., 2006;Hofmann and Ott, 1980;Lin et al., 2014;Wasson, 1962), and is currently used as a traditional medicine for the treatment ofsymptoms such as anemia, headache, rheumatism and diarrhoea (Casselman et al., 2014;Lin et al., 2014;Valdés et al., 1983). It is taken in various ways such as chewing the fresh leaves, drinking the extracts of the leaves or smoking dry leaves to obtain its hallucinatory effects (González et al., 2006). ...
... Among the species having adverse effects, Salvia divinorum (Epling and Javita), a member of the Lamiaceae (Labiatae) family, is endemic to the northern Sierra Mazateca mountain of Mexico. It was used by Mazatec Indians in spiritual rituals to have hallucinatory effects (Bertea et al., 2005;Bertea et al., 2006;Hofmann and Ott, 1980;Lin et al., 2014;Wasson, 1962), and is currently used as a traditional medicine for the treatment ofsymptoms such as anemia, headache, rheumatism and diarrhoea (Casselman et al., 2014;Lin et al., 2014;Valdés et al., 1983). It is taken in various ways such as chewing the fresh leaves, drinking the extracts of the leaves or smoking dry leaves to obtain its hallucinatory effects (González et al., 2006). ...
... Similarly, in an in vivo study, salvinorin B MOM was also stated as a potent KOR agonist against a KOR . As tens of different terpenoids are found in S. divinorum plant (Casselman et al., 2014;Lin et al., 2014;Valdés et al., 1983), similarly, it is highly expected that several different derivatives of salvinorin B molecules might also present in these plants with high salvinorin B, content including S. potentillifolia, S. adenocaulon and S. cryptantha species. In another study, Salvia species (S. tomentosa, S. tchihatcheffii, S. rosifolia, S. dichroantha and S. sclarea) were collected from different regions in Turkey and their opioid receptor binding capacities were tested, in vitro. ...
Introduction:
Salvia, an important and widely available member of Lamiaceae family. Although comparative analysis on secondary metabolites in several Salvia species from Turkey has been reported, their hallucinogenic chemicals have not been screened thoroughly.
Objective:
This study provides LC-MS/MS analysis of 40 Salvia species for screening their psychoactive constituents of salvinorin A and salvinorin B. 5S-rRNA gene non-coding region of Salvia plants was sequenced, aligned and compared with that sequence of Salvia divinorum plant.
Methodology:
Targeted molecules of salvinorin A and salvinorin B were quantified, using LC-MS/MS, from all aerial parts of 40 Salvia species, collected from different parts of Turkey. Regions of 5S-rRNA gene from different species were amplified by polymerase chain reaction and DNA sequences were aligned with Salvia divinorum DNA sequences.
Results:
Very few of the Salvia species (S. recognita, S. cryptantha and S. glutinosa) contained relatively high levels of salvinorin A (212.86 ± 20.46 μg/g, 51.50 ± 4.95 μg/g and 38.92 ± 3.74 μg/g, respectively). Salvinorin B was also found in Salvia species of S. potentillifolia, S. adenocaulon and S. cryptantha as 2351.99 ± 232.22 μg/g, 768.78 ± 75.90 μg/g and 402.24 ± 39.71 μg/g, respectively. The sequences of 5S-rRNA gene of 40 different Salvia species were presented and it was found that none of the Salvia species in Turkey had similar DNA sequence to Salvia divinorum plant.
Conclusion:
This is the first report of screening 40 Salvia species in Turkey according to their psychoactive constituents, salvinorin A and salvinorin B and their genomic structures. It is possible that some of these Salvia species may exhibit some psycho activity. Thus, they need to be screened further. Copyright © 2017 John Wiley & Sons, Ltd.
... Específicamente, se vende en sitios web como hojas secas, extractos u otras preparaciones que prometen la experimentación de sus efectos (ver figura 2) [1,3,16,18]. Cabe resaltar que existen páginas web que proporcionan todo tipo de información respecto a la planta, como es el caso de su compra y consumo, además de la explicación de sus efectos en determinadas cantidades [8,20]. [20] Legalidad Se conocen diferentes posturas respecto a la legalización de la venta, compra y consumo de Salvia divinorum E&J. ...
... Cabe resaltar que existen páginas web que proporcionan todo tipo de información respecto a la planta, como es el caso de su compra y consumo, además de la explicación de sus efectos en determinadas cantidades [8,20]. [20] Legalidad Se conocen diferentes posturas respecto a la legalización de la venta, compra y consumo de Salvia divinorum E&J. Por un lado, los científicos afirman que sus componentes tienen un gran potencial para estudios farmacológicos, además de tener una baja toxicidad y no presentar efectos adictivos en el organismo. ...
... En Noruega, Finlandia, Estonia e Islandia, es legal el uso de la planta con fines medicinales y solo puede ser obtenida con prescripción médica. Por ejemplo, se utiliza para el tratamiento de personas dependientes a la cocaína y a la heroína [4,8,9,15,[20][21][22][23][24][25][26]. ...
Resumen. Tema y alcance: el objetivo de esta revisión es presentar los estudios químicos que se han realizado sobre Salvia divinorum E&J en estos últimos años. Características: desde la década de 1990 hasta hoy se ha incrementado la distribución y el uso de Salvia divinorum E&J para “fines recreativos”, debido a sus efectos alucinógenos y a su fácil acceso. Sus efectos en el organismo se han relacionado con las de otras sustancias como: delta-9- thc en la marihuana, dmt, lsd, mdma, pcp y ketamina. Hallazgos: las investigaciones químicas realizadas en otros países sobre Salvia divinorum E&J se enfocan en los procesos de extracción, determinación, cuantificación, análisis y biosíntesis de Salvinorina A, compuesto químico al cual se le atribuye la bioactividad de la planta. Este compuesto es considerado como uno de los alucinógenos más potentes de origen natural, además de ser química y estructuralmente único, puesto que fue el primer diterpeno conocido con actividad psicoactiva. Conclusiones: la presente revisión encontró que en los últimos años las investigaciones químicas en Salvia divinorum E&J están enfocadas a través del uso de cromatografía de gases y cromatografía líquida en diversas matrices como hojas, sangre, orina y agua, con el fin de determinar la Salvinorina A y otros metabolitos presentes en la planta. En una de las investigaciones, comprobaron por rmn y hr-esi-ms que la biosíntesis de Salvinorina A está dada por la ruta metabólica del ácido mevalónico y la ruta del metileritritol fosfato, las cuales corresponden a las rutas metabólicas para la biosíntesis de terpenos.
... In recent years, the UNODC has warned the emergence of new psychoactive substances (NPS) [8,9]. NPS are classified by the UNODC as synthetic cannabinoids, synthetic cathinones, ketamine and PCP-type substances, phenethylamines, piperazines, tryptamines, aminoindanes, plant-based substances and others [10]. ...
... Other NPS of natural origin have also been identified. For example, Salvia has been available from the internet in Taiwan while Kratom has been confiscated in Korea [8]. Both have not been listed as controlled substances by the United Nations Conventions. ...
Background:
Illegal drug use has long been a global concern. Taiwan and Korea are geographically adjacent and both countries have experienced the illegal use problems of methamphetamine, a predominant prototype of New Psychoactive Substances (NPS). NPS, a term coined by the United Nations Office on Drugs and Crime (UNODC) in recent years, have not been scrutinized for their safety and may become a new threat to public health and security worldwide. To conduct evidence-based drug policy, it is imperative to estimate the trend and pattern of illegal drug use. Therefore, this study aims to analyze and compare the current status of drug-related seizures, arrests and illegal drug use, with a focus on methamphetamine and NPS, between Taiwan and Korea.
Methods:
Data of illegal drug (including NPS)-related seizures and arrests were collected via anti-drug related agencies of both countries from 2006 through 2014.Since listing of NPS as controlled substances was a result of NPS abuse liability through official evaluation, the items of controlled NPS were used as an indicator of emerging use. These data obtained from Taiwan and Korea was then compared.
Results:
The results showed that while methamphetamine remained as a predominant drug in both Taiwan and Korea for decades, different illegal drug use patterns have been observed in these two countries. In Taiwan, the major illegal drugs were methamphetamine, heroin, and ketamine, whereas in Korea those were methamphetamine and cannabis. By comparison of per capita illicit drug seizures, the illegal drug use situation in Taiwan was at a higher stake than that in Korea. In terms of NPS use, ketamine has been a major drug in Taiwan, but it was seldom found in Korea. Besides ketamine, the major type of NPS was synthetic cathinones in Taiwan whereas it was synthetic cannabinoids and phenethylamines in Korea. The difference in the numbers of controlled NPS items between Taiwan (23) and Korea (93) may be due to the implementation of temporary control on NPS in Korea since 2011.
Conclusion:
While the problem of methamphetamine still lingers, NPS have emerged as a new issue in both countries. However, the NPS pattern was different between Taiwan and Korea. Although the controlled NPS items in Taiwan were far less than those in Korea, the quantity of total NPS seizures, especially with ketamine, was much larger in Taiwan than in Korea. Different NPS pattern may also imply they were from different sources. Factors other than geographical proximity, such as drug policy and availability and accessibility to drugs, should be taken into account for the current status of illegal drug use in Korea and Taiwan.
The salvinorins serve as templates for next generation analgesics, antipruritics, and dissociative hallucinogens via selective and potent agonism of the kappa-opioid receptor (KOR). In contrast to most opioids, the salvinorins lack basic amines and bind with high affinity and selectivity via complex polyoxygenated scaffolds that have frustrated deep-seated modification by synthesis. Here we describe a short asymmetric synthesis that relies on a sterically confined organocatalyst to dissociate acidity from reactivity and effect Robinson annulation of an unactivated nucleophile/unstable electrophile pair. Combined with a cobalt-catalyzed polarized diene-alkyne cycloaddition, the route allows divergent access to a focused library of salvinorins. We appraise the synthesis by its generation of multiple analogs that exceed the potency, selectivity, stability, and functional bias of salvinorin A itself.
