RS-102221: A Novel High Affinity and Selective, 5-HT 2C Receptor Antagonist

Bonhaus, Douglas W.; Weinhardt, Klaus K.; Taylor, Marianne; Desouza, Arun H. G.; McNeeley, P. M.; Szczepanski, Krystine; Fontana, David; Trinh, Jane V; Rocha, Cindy; Dawson, M. W.; Flippin, Lee A.; Eglen, Richard M.

doi:10.1016/s0028-3908(97)00049-x

Cited by 228 publications

(155 citation statements)

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“…Fourth, at doses producing robust increases of extracellular norepinephrine and dopamine levels in the frontal cortex of freely-moving rats, and which abolish 5-HT 2C receptor-mediated DS and penile erections, both SB206,553 and SB242,084 (Kennett et al 1997;Millan et al 1997;Dekeyne et al 1999;Gobert et al 2000), did not generalize to MDL100,907. A further, novel 5-HT 2C antagonist, RS102221 (Bonhaus et al 1997) also did not generalize. Fifth, SB206,553 is a potent antagonist at 5-HT 2B as well as 5-HT 2C receptors (Kennett et al 1996), and a further (selective) antagonist at this site, SB204,741 (Forbes et al 1995;Dekeyne et al 1999), similarly did not generalize to MDL100,907.…”

Section: Discussionmentioning

confidence: 93%

“…We also characterized the role of 5-HT 2A as compared with 5-HT 2B and 5-HT 2C receptors in the mediation of its potential DS properties. Generalization testing was conducted with a further selective and potent antagonist at 5-HT 2A receptors, SR46349 (Rinaldi-Carmona et al 1992), the 5-HT 2B/2C antagonist, SB206,553 (Kennett et al 1996), the selective 5-HT 2B antagonist, SB204,741 (Forbes et al 1995), and the novel selective 5-HT 2C antagonists, RS102221 and SB242,084 (Bonhaus et al 1997;Kennett et al 1997).…”

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confidence: 99%

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The Selective Serotonin2A Receptor Antagonist, MDL100,907, Elicits a Specific Interoceptive Cue in Rats

Dekeyne

2002

Neuropsychopharmacology

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Employing a two-lever, food-reinforced, Fixed Ratio 10 drug discrimination procedure, rats were trained to recognize the highly-selective serotonin (5-HT) 2A receptor antagonist, MDL100,907 (0.16 mg/kg, i.p.) Drug discrimination procedures have been extensively used in the characterization of psychoactive agents, including drugs interacting with 5-HT reuptake sites (Millan et al. 1999b) and agonists at 5-HT 1A (Schreiber et al. 1995b) and 5-HT 3 (Glennon et al. 1992) receptors. Although it has proven difficult to differentiate the roles of closely-related 5-HT 2A , 5-HT 2B and 5-HT 2C receptors (Glennon 1991), it was suggested that discriminative stimulus (DS) properties of several 5-HT 2 agonists and hallucinogens, such as mescaline (Appel and Callahan 1989), lysergic acid diethylamide (LSD) (Fiorella et al. 1995) and quipazine (Friedman et al. 1984), are mediated by 5-HT 2A receptors. Further, use of the highly selective 5-HT 2A receptor antagonist, MDL100,907 (Kehne et al. 1996), demonstrated that 5-HT 2A receptors mediate DS properties of 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI), a further hallucinogen (Schreiber et al. 1994). In contrast, DS properties of the 5-HT 2 ligand, m-chlorophenylpiperazine (mCPP), appear to be mediated by 5-HT 2C receptors (Callahan and Cunningham 1994; see Gommans et al. 1998), and employing the 5-HT 2B/2C antagonist, SB206,553, and the selective 5-HT 2C antagonist, SB242,084, it was shown that 5-HT 2C receptors likewise mediate DS properties of the novel, mixed 5-HT 2C/2B agonist, RO60,0175 ((S)-2-(6-chloro-5-fluoroindol-1-yl)-1-methylethylamine; Dekeyne et al. 1999).Interest in 5-HT 2A receptors has been reinforced by evidence that their blockade may contribute to the distinctive functional profile of the "atypical" antipsychotic, clozapine, and, possibly, other novel agents employed

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Section: Discussionmentioning

confidence: 93%

mentioning

confidence: 99%

The Selective Serotonin2A Receptor Antagonist, MDL100,907, Elicits a Specific Interoceptive Cue in Rats

Dekeyne

2002

Neuropsychopharmacology

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“…However, antagonism at the 5-HT 2C receptor can increase food intake and body weight in rats (Bonhaus et al, 1997), thus this may not be an advantageous strategy for treatment in patients as weight gain is a major adverse effect and could affect compliance (see Allison et al, 1999 for meta-analysis).…”

Section: Effect Of Sb-243213amentioning

confidence: 99%

Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat

et al. 2009

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“…Ketanserin, a 5-HT 2A/2B/2C receptor antagonist, RS-102221, a selective 5-HT 2C receptor antagonist (Bonhaus et al, 1997) and LY-272015, a selective 5-HT 2B receptor antagonist (Cohen et al, 1996), were used to con®rm the selective e ects of the agonist ligands. Application of these antagonists produced no e ect on the ongoing or evoked activity of the cells.…”

Section: Effects Of 5-ht 2 Receptor Antagonists On Doi Mk-212 and Bwmentioning

confidence: 99%

In vivo modulation of vagal‐identified dorsal medullary neurones by activation of different 5‐Hydroxytryptamine₂ receptors in rats

Sévoz‐Couche¹,

Spyer²,

Jordan³

2000

British J Pharmacology

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1 In in vivo experiments, DOI (a 5-HT 2 receptor agonist), MK-212 (a 5-HT 2C receptor agonist), and BW-723C86 (a 5-HT 2B receptor agonist) were applied by ionophoresis to neurones in the rat nucleus tractus solitarius (NTS) receiving vagal a erent input. 2 The majority of the putative`monosynaptically' vagal activated cells were inhibited by both MK-212 (4/6) and DOI (2/4), but una ected by . In contrast,`polysynaptically' activated NTS cells were excited by both BW-723C86 (13/19) and DOI (9/10). Inactive`intermediate' cells were inhibited by BW-723C86 (9/12), MK-212 (5/6) and DOI (3/4), whilst active cells of this group were excited by BW-723C86 (7/13) and DOI (5/5). 3 The selective 5-HT 2B receptor antagonist LY-202715 signi®cantly reduced the excitatory actions of BW-723C86 on`intermediate' and`polysynaptic' cells (13/13), but not the inhibitory e ects observed on inactive Group 2 cells (n=5) whereas the selective 5-HT 2C receptor antagonist RS-102221 reversed the inhibitory e ects of MK-212 and DOI on`monosynaptic and`intermediate' neurones. 4 Cardio-pulmonary a erent stimulation inhibited two of four putative`monosynaptically' activated calls and all four inactive intermediate cells. These were also inhibited by DOI and MK-212. In contrast, cardio-pulmonary a erents excited all ®ve active intermediate cells and all six putative`polysynaptically' activated NTS cells, while all were also previously excited by BW-723C86 and/or DOI. 5 In conclusion, these data demonstrate that neurones in the NTS are a ected di erently by 5-HT 2 receptor ligands, in regard of their vagal postsynaptic location, the type of cardio-pulmonary a erent they receive and the di erent 5-HT 2 receptors activated.

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RS-102221: A Novel High Affinity and Selective, 5-HT 2C Receptor Antagonist

Cited by 228 publications

References 46 publications

The Selective Serotonin2A Receptor Antagonist, MDL100,907, Elicits a Specific Interoceptive Cue in Rats

The Selective Serotonin2A Receptor Antagonist, MDL100,907, Elicits a Specific Interoceptive Cue in Rats

Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat

In vivo modulation of vagal‐identified dorsal medullary neurones by activation of different 5‐Hydroxytryptamine₂ receptors in rats

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RS-102221: A Novel High Affinity and Selective, 5-HT 2C Receptor Antagonist

Cited by 228 publications

References 46 publications

The Selective Serotonin2A Receptor Antagonist, MDL100,907, Elicits a Specific Interoceptive Cue in Rats

The Selective Serotonin2A Receptor Antagonist, MDL100,907, Elicits a Specific Interoceptive Cue in Rats

Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat

In vivo modulation of vagal‐identified dorsal medullary neurones by activation of different 5‐Hydroxytryptamine2 receptors in rats

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Product

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In vivo modulation of vagal‐identified dorsal medullary neurones by activation of different 5‐Hydroxytryptamine₂ receptors in rats