Abstract
A series of 2-(aminoalkyl)naphth[1,8-cd]isothiazole 1,1-dioxides was synthesized and examined in various receptor binding tests. Most compounds demonstrated high affinity for the 5-HT2 receptor with moderate to high selectivity. A member of this series, compound 24 (RP 62203), displays high 5-HT2 receptor affinity (Ki = 0.26 nM), which is respectively more than 100 and 1000 times higher than its affinity for alpha 1 (Ki = 38 nM) and D2 (Ki greater than 1000 nM) receptors. This compound is a potent orally effective and long lasting 5-HT2 antagonist in the mescaline-induced head-twitches test in mice and rats.
MeSH terms
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Animals
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Behavior, Animal / drug effects
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Chemical Phenomena
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Chemistry
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Cyclic S-Oxides / chemical synthesis*
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Cyclic S-Oxides / metabolism
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Cyclic S-Oxides / pharmacology
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Male
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Mescaline / pharmacology
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Mice
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Molecular Structure
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Naphthalenes / chemical synthesis*
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Naphthalenes / metabolism
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Naphthalenes / pharmacology
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Piperidines / metabolism
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Piperidines / pharmacology
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Rats
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Rats, Inbred Strains
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Receptors, Serotonin / metabolism
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Ritanserin
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Serotonin Antagonists / chemical synthesis*
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Serotonin Antagonists / metabolism
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Serotonin Antagonists / pharmacology
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Structure-Activity Relationship
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Thiazoles / chemical synthesis*
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Thiazoles / metabolism
Substances
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Cyclic S-Oxides
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Naphthalenes
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Piperidines
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Receptors, Serotonin
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Serotonin Antagonists
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Thiazoles
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Ritanserin
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fananserin
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Mescaline