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- Title
Differences in potency and efficacy of a series of phenylisopropylamine/phenylethylamine pairs at 5-HT[sub 2A] and 5-HT[sub 2C] receptors.
- Authors
Villalobos, Claudio; Moya, Pablo R.; Cassels, Bruce K.; Huidobro-Toro, J, Pablo; Acuña-Castillo, Claudio; Sáez, Patricio
- Abstract
1 The pharmacological profile of a series of (± )-2,5-dimethoxy-4-(X)-phenylisopropylamines (X = I, Br, NO[sub2]. CH[sub3]. or H) and corresponding phenylethylamines, was determined in Xenopus laevis oocytes injected with cRNA coding for rat 5-HT[sub2A] or 5-HT[sub2c]- receptors. The efficacy and relative potency of these drugs were determined, and compared to classical 5-HT[sub2] receptor agonists and antagonists. 2 The rank order of agonist potency at the 5-HT[sub2A] receptor was; α-meihyI-5-HT = 5-HT>m-CPP>MK-212: at the 5-HT[sub2C]- receptor the order was; 5-HT>α-methyl-5-HT>MK.-212>m-CPP. All these compounds were full agonists at the 5-HT[sub2C] receptor, but α-melhyl-5-HT and m-CPP showed lower efficacy at the 5-HT[sub2A] receptor. 3 4-(4-Fluorobenzoyl)-(4-phenylbutyl)piperidine (4F 4PP) was 200 times more potent as a 5-HT[sub2A] antagonist than at 5-HT[sup2C] receptors. Conversely. RS 102221 was 100 times more potent as a 5-HT[sub2C] antagonist, continuing their relative receptor selectivities. 4 The phenylisopropylamines were partial agonists at the 5-HT[sub2A] receptor, with I[sub max] 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-HT[sub2C] receptors; DOI was a full 5-HT[sub2C] agonist. 2C-1 and the other phenylethylamines examined showed relative efficacies at the 5-HT[sub2C] receptor ranging from 44±10% to 76±16%. 5 2C-N was a 5-HT[sub2] receptor antagonist; the mechanism was competitive at the 5-HT[sub2A] but non-competitive at the 5-HT[sub2C] receptor. The antagonism was time-dependent at the 5-HT[sub2c]receptor but independent of pre-incubation time at the 5-HT[sub2A] receptor subtype. 6 The α-methyl group determines the efficacy of these phenylalkylamines at the 5-HT[sub2A] and 5-HT[sub2C] receptors.
- Subjects
HALLUCINOGENIC drugs; PHENETHYLAMINES; SEROTONIN agonists; SEROTONIN antagonists; XENOPUS laevis
- Publication
British Journal of Pharmacology, 2002, Vol 136, Issue 4, p510
- ISSN
0007-1188
- Publication type
Article