The metabolism of lysergic acid di[14C]ethylamide ([14C]LSD) in the isolated perfused rat liver

Siddik, Zahid H.; Barnes, Roger D.; Dring, L. G.; Smith, Robert L.; Williams, R. T.

doi:10.1016/0006-2952(79)90617-8

Cited by 16 publications

(8 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compared to LSD, in the mass spectrum resulting from the precursor ion of m / z 340 all major fragments were shifted by 16 u indicating a hydroxylation on the tetracyclic ring system (Figure B). Two HO‐LSD isomers hydroxylated in positions 13 and 14 on the indole moiety were proposed from initial metabolism studies in rats . In humans, presence of either 13‐ or 14‐HO‐LSD as definite chemical structure has never been proven.…”

Section: Resultsmentioning

confidence: 99%

“…Two HO-LSD isomers hydroxylated in positions 13 and 14 on the indole moiety were proposed from initial metabolism studies in rats. [43,44] In humans, presence of either 13-or 14-HO-LSD as definite chemical structure has never been proven. Previous studies in human urine could only identify one peak for HO-LSD without conclusive structure elucidation 11 .…”

Section: Initial Screening For Lsd Metabolitesmentioning

confidence: 99%

See 1 more Smart Citation

Development and validation of an ultra‐fast and sensitive microflow liquid chromatography‐tandem mass spectrometry (MFLC‐MS/MS) method for quantification of LSD and its metabolites in plasma and application to a controlled LSD administration study in humans

Steuer

Poetzsch

Stock

et al. 2016

Drug Testing and Analysis

View full text Add to dashboard Cite

Lysergic acid diethylamide (LSD) is a semi-synthetic hallucinogen that has gained popularity as a recreational drug and has been investigated as an adjunct to psychotherapy. Analysis of LSD represents a major challenge in forensic toxicology due to its instability, low drug concentrations, and short detection windows in biological samples. A new, fast, and sensitive microflow liquid chromatography (MFLC) tandem mass spectrometry method for the validated quantification of LSD, iso-LSD, 2-oxo 3-hydroxy-LSD (oxo-HO-LSD), and N-desmethyl-LSD (nor-LSD) was developed in plasma and applied to a controlled pharmacokinetic (PK) study in humans to test whether LSD metabolites would offer for longer detection windows. Five hundred microlitres of plasma were extracted by solid phase extraction. Analysis was performed on a Sciex Eksigent MFLC system coupled to a Sciex 5500 QTrap. The method was validated according to (inter)-national guidelines. MFLC allowed for separation of the mentioned analytes within 3 minutes and limits of quantification of 0.01 ng/mL. Validation criteria were fulfilled for all analytes. PK data could be calculated for LSD, iso-LSD, and oxo-HO-LSD in all participants. Additionally, hydroxy-LSD (HO-LSD) and HO-LSD glucuronide could be qualitatively detected and PK determined in 11 and 8 subjects, respectively. Nor-LSD was only sporadically detected. Elimination half-lives of iso-LSD (median 12 h) and LSD metabolites (median 9, 7.4, 12, and 11 h for oxo-HO-LSD, HO-LSD, HO-LSD-gluc, and nor-LSD, respectively) exceeded those of LSD (median 4.2 h). However, screening for metabolites to increase detection windows in plasma seems not to be constructive due to their very low concentrations. Copyright © 2016 John Wiley & Sons, Ltd.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Initial Screening For Lsd Metabolitesmentioning

confidence: 99%

Development and validation of an ultra‐fast and sensitive microflow liquid chromatography‐tandem mass spectrometry (MFLC‐MS/MS) method for quantification of LSD and its metabolites in plasma and application to a controlled LSD administration study in humans

Steuer

Poetzsch

Stock

et al. 2016

Drug Testing and Analysis

View full text Add to dashboard Cite

show abstract

“…Dihydroxy-LSD is probably identical to 2-oxo-3hydroxy-LSD (O-H-LSD), which is believed to be the main metabolite of LSD in humans (Poch et al 1999;Johansen and Jensen 2005;Favretto et al 2007;Dolder et al 2015;Steuer et al 2017). N-Deethyl-LSD (lysergic acid monoethylamide, LAE-32) and N 6 -demethyl-LSD (nor-LSD) have been identified as metabolites of LSD in rats (Niwaguchi et al 1974;Siddik et al 1979b) and humans (Lim et al 1988;Cai and Henion 1996;Canezin et al 2001;Steuer et al 2017). Rats and humans are also known to metabolize LSD to 13-and 14-hydroxy-LSD and to the corresponding glucuronides (Siddik et al 1975(Siddik et al ,1979bCanezin et al 2001;Steuer et al 2017).…”

Section: Biotransformation Of Ald-52 and 1p-lsdmentioning

confidence: 99%

“…N-Deethyl-LSD (lysergic acid monoethylamide, LAE-32) and N 6 -demethyl-LSD (nor-LSD) have been identified as metabolites of LSD in rats (Niwaguchi et al 1974;Siddik et al 1979b) and humans (Lim et al 1988;Cai and Henion 1996;Canezin et al 2001;Steuer et al 2017). Rats and humans are also known to metabolize LSD to 13-and 14-hydroxy-LSD and to the corresponding glucuronides (Siddik et al 1975(Siddik et al ,1979bCanezin et al 2001;Steuer et al 2017). Hydroxy LSD isomers 1 and 2 are probably identical to 13-and 14-hydroxy-LSD but it was not possible to determine the position of the hydroxy groups based on fragmentation patterns.…”

Section: Biotransformation Of Ald-52 and 1p-lsdmentioning

confidence: 99%

Pharmacological and biotransformation studies of 1-acyl-substituted derivatives of -lysergic acid diethylamide (LSD)

et al. 2020

View full text Add to dashboard Cite

The ergoline d-lysergic acid diethylamide (LSD) is one of the most potent psychedelic drugs. 1-Acetyl-LSD (ALD-52), a derivative of LSD containing an acetyl group on the indole nitrogen, also produces psychedelic effects in humans and has about the same potency as LSD. Recently, several other 1-acyl-substitued LSD derivatives, including 1-propanoyl-LSD (1P-LSD) and 1butanoyl-LSD (1B-LSD), have appeared as designer drugs. Although these compounds are assumed to act as prodrugs for LSD, studies have not specifically tested this prediction. The present investigation was conducted to address the gap of information about the pharmacological effects and mechanism-of-action of 1-acyl-substituted LSD derivatives. Competitive binding studies and calcium mobilization assays were performed to assess the interaction of ALD-52, 1P-LSD, and 1B-LSD with serotonin 5-HT 2 performed with 1B-LSD to assess its binding to othe (HTR) studies were performed in C57BL/6J mice to assess in vivo activation of 5-HT 2A (the receptor thought to be primarily responsible for ha chromatography/ion-trap mass spectrometry (LC/MS) was used to quantify plasma levels of LSD in Sprague-Dawley rats treated with ALD-52 and affinity of LSD for most monoamine receptors, inclu 2A sites, by one to two orders of magnitude. Although LSD acts as an agonist at 5-HT 2 subtypes, ALD-52, 1P-LSD and 1B-LSD had weak efficacy or acted as antagonists in Ca 2+-mobilization assays. Despite the detrimental effect of 1-acyl substitution on 5-HT 2A atives induce head twitches in mice with relatively high potency. High levels of LSD were detected in the plasma of rats after subcutaneous administration of ALD-52 and 1P-LSD, demonstrating ted in vivo. These findings are consistent with the prediction that ALD-52, 1P-LSD and 1B-LSD serve as pro-drugs for LSD. receptor subtypes. A receptorome screening was r potential targets. Head twitch response llucinogenesis). Finally, liquid 1P-LSD. 1-Acyl-substitution reduced the ding 5-HT affinity and efficacy, 1-acyl-substitued LSD deriv these compounds are rapidly and efficiently deacyla

show abstract

“…Minor oxidation metabolites such as 2-oxo and 12-hydroxy were also identified. Metabolites derived from dealkylation at the carboxylamide side chain and at the piperidine N-6 position were also observed [64][65][66][67].…”

Section: Ergot Alkaloidsmentioning

confidence: 99%

Dopamine Agonists in the Treatment of Parkinsons Disease-Past, Present and Future

Sit

2000

CPD

View full text Add to dashboard Cite

An attempt is made by the author to highlight the important events that laid the foundation of dopamine agonists as a treatment strategy for Parkinson s disease. This debilitating neurodegenerative disorder is long recognized as a result of progressive cell loss in the substantia nigra of the midbrain. The destruction of dopaminergic neurons with projections to the striatum results in the diminishing striatal dopamine levels. Anticholinergic drugs were once widely used to counteract the relative overactivity of cholinergic output from the basal ganglia and the strategy was only met with limited success. The discovery of dopamine depletion and the use of levodopa - a dopamine metabolic precursor, led the way to dopamine replacement therapy . The initial success with levodopa was soon overshadowed by the long-term side effects associated with levodopa. Many new drugs were developed with the hope to replace or strengthen the usefulness of levodopa. Apomorphine and ergot alkaloids have been around for some time; they are recently joined by newer dopamine agonists such as ropinirole and pramipexole. Each of these has its own characteristics and has occupied a place in the pharmacotherapy of Parkinson s disease. In this review older aporphines and ergot alkaloids are discussed first. More emphasis is directed to the side-effect profiles, metabolism and pharmacokinetics in terms of their unique chemical structures. The most recent agonists will be briefly discussed before we move on to the future - the future of emerging novel classes of promising dopaminergic agonists.

show abstract

The metabolism of lysergic acid di[14C]ethylamide ([14C]LSD) in the isolated perfused rat liver

Cited by 16 publications

References 33 publications

Development and validation of an ultra‐fast and sensitive microflow liquid chromatography‐tandem mass spectrometry (MFLC‐MS/MS) method for quantification of LSD and its metabolites in plasma and application to a controlled LSD administration study in humans

Development and validation of an ultra‐fast and sensitive microflow liquid chromatography‐tandem mass spectrometry (MFLC‐MS/MS) method for quantification of LSD and its metabolites in plasma and application to a controlled LSD administration study in humans

Pharmacological and biotransformation studies of 1-acyl-substituted derivatives of -lysergic acid diethylamide (LSD)

Dopamine Agonists in the Treatment of Parkinsons Disease-Past, Present and Future

Contact Info

Product

Resources

About