A-Ring Ortho-Disubstituted Aporphine Derivatives as Potential Agonists or Antagonists at Serotonergic 5-HT1A Receptors

Cannon, Joseph G.; Flaherty, Patrick; Özkutlu, Uǧur; Long, J. P.

doi:10.1021/jm00011a002

Cited by 18 publications

(12 citation statements)

References 2 publications

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“…The presence of this alkaloid might explain anecdotal reports of “vivid dreams” and opioid-like activities observed in patients taking black cohosh [67], as well as explain its observed in vitro opioid activity [68]. Aporphine alkaloids exhibit strong serotonergic activity against the 5-HT 1A receptor [69, 70]. For example, N -methyllaurotetanine, which is an N -methyl analog of laurotetanine identified in this study, is a potent ligand for the 5-HT 1A receptor [70].…”

Section: Resultsmentioning

confidence: 99%

Mass spectrometric dereplication of nitrogen-containing constituents of black cohosh (Cimicifuga racemosa L.)

et al. 2012

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Black cohosh preparations are popular dietary supplements among women seeking alternative treatments for menopausal complaints. For decades, triterpene glycosides and phenolic acids have dominated the phytochemical and biomedical research on this plant. In this study, we provide evidence that black cohosh contains an unexpected and highly diverse group of secondary nitrogenous metabolites previously unknown to exist in this plant. Using a dereplication approach that combines accurate mass measurements, database searches and general knowledge of biosynthetic pathways of natural products, we identified or tentatively identified 73 nitrogen-containing metabolites, many of which are new natural products. The identified compounds belong to several structural groups including alkaloids, amides or esters of hydroxycinnamic acids and betains. Among the alkaloids, several classes such as guanidino alkaloids, isoquinolines and β-carbolines were identified. Fragmentation patterns for major compound classes are discussed, which provides a framework for the discovery of these compounds from other sources. Identification of alkaloids as a well-known group of bioactive natural products represents an important advance in better understanding of the pharmacological profile of black cohosh.

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Section: Resultsmentioning

confidence: 99%

Mass spectrometric dereplication of nitrogen-containing constituents of black cohosh (Cimicifuga racemosa L.)

et al. 2012

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“…This is especially necessary in light of the fact that series of aporphine enantiomers have been shown to have opposing effects (agonism and antagonism) at the related 5-HT 1A receptor. 11, 31, 32 …”

Section: Resultsmentioning

confidence: 99%

New aporphinoid 5-HT2A and α1A antagonists via structural manipulations of nantenine

Chaudhary¹,

Ponnala²,

LeGendre³

et al. 2011

Bioorganic & Medicinal Chemistry

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A series of C1, C2, C3 and N6 analogs of nantenine (2) was synthesized and evaluated in 5-HT2A and α1A receptor functional assays. Alkyl substitution of the C1 and N6 methyl groups of nantenine provided selective 5-HT2A and α1A antagonists respectively. The C2 alkyloxy analogs studied were generally selective for α1A vs 5-HT2A. The C3 bromo analog 15 is one of the most potent aporphinoid 5-HT2A antagonists known presently.

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“…In fact, the indoline 48 displayed an astounding 5-HT 1A selectivity for a compound of this class. Cannon et al [70,71] published the 10-methyl substituted derivative of 49, (R)-(-)-10-methyl-11-hydroxyaporphine, (50 MHA) in an effort to further study structure-activity relationships (SAR) of (R)-aporphines at DA receptors (Fig. 12).…”

Section: Ki (Nm)mentioning

confidence: 99%

Derivatives as 5HT1A Receptor Ligands-Past and Present

Caliendo¹,

Santagada²,

Perissutti³

et al. 2005

CMC

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Serotonin is a neuromediator, well-know for its implication in mood regulation, anxiety, depression and, insomnia as well as in normal human function such as sleep, sexual activity and appetite. In this way, serotonin (5-hydroxytryptamine, 5-HT) is one of the most attractive targets for medicinal chemists and pharmaceutical companies. Among 5-HTRs, the 5-HT1A subtype is the best studied, and it is generally accepted that it is involved in psychiatric disorders such as anxiety and depression. Several structurally different compounds are known to bind 5-HT1A receptor sites such as aminotetralins, ergolines, arylpiperazines, indolylalkylamines, aporphines and aryloxyalkyl-amines. In this review, we report an overview of the 5-HT1A receptor ligands, belonging to different chemical classes.

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A-Ring Ortho-Disubstituted Aporphine Derivatives as Potential Agonists or Antagonists at Serotonergic 5-HT1A Receptors

Cited by 18 publications

References 2 publications

Mass spectrometric dereplication of nitrogen-containing constituents of black cohosh (Cimicifuga racemosa L.)

Mass spectrometric dereplication of nitrogen-containing constituents of black cohosh (Cimicifuga racemosa L.)

New aporphinoid 5-HT2A and α1A antagonists via structural manipulations of nantenine

Derivatives as 5HT1A Receptor Ligands-Past and Present

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