Details

Autor(en) / Beteiligte

• Acuña‐Castillo, Claudio
• Villalobos, Claudio
• Moya, Pablo R
• Sáez, Patricio
• Cassels, Bruce K
• Huidobro‐Toro, J Pablo

Titel

Differences in potency and efficacy of a series of phenylisopropylamine/phenylethylamine pairs at 5‐HT2A and 5‐HT2C receptors

Ist Teil von

• British journal of pharmacology, 2002-06, Vol.136 (4), p.510-519

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2002

Link zum Volltext

Quelle

Wiley Online Library

Beschreibungen/Notizen

• The pharmacological profile of a series of (±)‐2,5‐dimethoxy‐4‐(X)‐phenylisopropylamines (X=I, Br, NO2, CH3, or H) and corresponding phenylethylamines, was determined in Xenopus laevis oocytes injected with cRNA coding for rat 5‐HT2A or 5‐HT2C receptors. The efficacy and relative potency of these drugs were determined and compared to classical 5‐HT2 receptor agonists and antagonists. The rank order of agonist potency at the 5‐HT2A receptor was: α‐methyl‐5‐HT=5‐HT>m‐CPP>MK‐212; at the 5‐HT2C receptor the order was: 5‐HT>α‐methyl‐5‐HT>MK‐212>m‐CPP. All these compounds were full agonists at the 5‐HT2C receptor, but α‐methyl‐5‐HT and m‐CPP showed lower efficacy at the 5‐HT2A receptor. 4‐(4‐Fluorobenzoyl)‐1‐(4‐phenylbutyl)piperidine (4F 4PP) was 200 times more potent as a 5‐HT2A antagonist than at 5‐HT2C receptors. Conversely, RS 102221 was 100 times more potent as a 5‐HT2C antagonist, confirming their relative receptor selectivities. The phenylisopropylamines were partial agonists at the 5‐HT2A receptor, with Imax relative to 5‐HT in the 22±7 to 58±15% range; the corresponding phenylethylamines had lower or undetectable efficacies. All these drugs had higher efficacies at 5‐HT2C receptors; DOI was a full 5‐HT2C agonist. 2C‐I and the other phenylethylamines examined showed relative efficacies at the 5‐HT2C receptor ranging from 44±10% to 76±16%. 2C‐N was a 5‐HT2 receptor antagonist; the mechanism was competitive at the 5‐HT2A, but non‐competitive at the 5‐HT2C receptor. The antagonism was time‐dependent at the 5‐HT2C receptor but independent of pre‐incubation time at the 5‐HT2A receptor subtype. The α‐methyl group determines the efficacy of these phenylalkylamines at the 5‐HT2A and 5‐HT2C receptors. British Journal of Pharmacology (2002) 136, 510–519; doi:10.1038/sj.bjp.0704747