Evaluation of structural effects on 5-HT(2A) receptor antagonism by aporphines: identification of a new aporphine with 5-HT(2A) antagonist activity. 2014

Shashikanth Ponnala, and Junior Gonzales, and Nirav Kapadia, and Hernan A Navarro, and Wayne W Harding
Chemistry Dept., Hunter College, CUNY, 695 Park Avenue, NY 10065, USA.

A set of aporphine analogs related to nantenine was evaluated for antagonist activity at 5-HT2A and α1A adrenergic receptors. With regards to 5-HT2A receptor antagonism, a C2 allyl group is detrimental to activity. The chiral center of nantenine is not important for 5-HT2A antagonist activity, however the N6 nitrogen atom is a critical feature for 5-HT2A antagonism. Compound 12b was the most potent 5-HT2A aporphine antagonist identified in this study and has similar potency to previously identified aporphine antagonists 2 and 3. The ring A and N6 modifications examined were detrimental to α1A antagonism. A slight eutomeric preference for the R enantiomer of nantenine was observed in relation to α1A antagonism.

UI MeSH Term Description Entries
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001060 Aporphines Dibenzoquinolines derived in plants from (S)-reticuline (BENZYLISOQUINOLINES).
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D044402 Receptor, Serotonin, 5-HT2A A serotonin receptor subtype found widely distributed in peripheral tissues where it mediates the contractile responses of variety of tissues that contain SMOOTH MUSCLE. Selective 5-HT2A receptor antagonists include KETANSERIN. The 5-HT2A subtype is also located in BASAL GANGLIA and CEREBRAL CORTEX of the BRAIN where it mediates the effects of HALLUCINOGENS such as LSD. Serotonin 2A Receptor,5-HT(2A) Receptor,5-HT2A Receptor,Receptor, Serotonin 2A,Serotonin 2A Receptors,5 HT2A Receptor,Receptor, 5-HT2A,Receptors, Serotonin 2A
D058830 Serotonin 5-HT2 Receptor Antagonists Drugs that bind to but do not activate SEROTONIN 5-HT2 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT2 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more specific 5-HT2 receptor subtypes. 5-HT2 Antagonist,5-HT2A Antagonist,5-HT2B Antagonist,5-HT2C Antagonist,Serotonin 5-HT2A Receptor Antagonists,Serotonin 5-HT2B Receptor Antagonists,Serotonin 5-HT2C Receptor Antagonists,5 HT2 Antagonist,5 HT2A Antagonist,5 HT2B Antagonist,5 HT2C Antagonist,Antagonist, 5-HT2,Antagonist, 5-HT2A,Antagonist, 5-HT2B,Antagonist, 5-HT2C,Serotonin 5 HT2 Receptor Antagonists,Serotonin 5 HT2A Receptor Antagonists,Serotonin 5 HT2B Receptor Antagonists,Serotonin 5 HT2C Receptor Antagonists

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