title: Irreversible blockade of central 5-HT binding sites by 8-methoxy-2'-chloro-PAT.
abstract: We have synthesized 8-methoxy-2-(N-2'-chloropropyl, N-propyl) aminotetralin (8-methoxy-2'-chloro-PAT), an alkylating agent derived from the potent 5-HT agonist, 8-hydroxy-2-(N,N-dipropyl)-aminotetralin (PAT). As expected for an irreversible ligand, the blockade of 3H-PAT or 3H-5-HT binding to post-synaptic 5-HT1 (A and B) sites in rat hippocampal membranes pretreated with 8-methoxy-2'-chloro-PAT could not be prevented by extensive washing of membranes. Prior occupancy of 5-HT1 sites by 5-HT or PAT prevented any subsequent irreversible blockade by the alkylating agent. Similar irreversible blockade by 8-methoxy-2'-chloro-PAT was found on 3H-PAT binding to striatal membranes suggesting that presynaptic 5-HT binding sites (see Gozlan et al., Nature, Lond. 305, 140, 1983) were sensitive also to the alkylating agent. In contrast, the modifying agent N-ethylmaleimide (NEM) reduced markedly 3H-PAT binding to postsynaptic hippocampal 5-HT1 sites, but did not alter 3H-PAT binding to striatal presynaptic 5-HT sites. Although 8-methoxy-2'-chloro-PAT bound irreversibly to different classes of 5-HT binding sites (5-HT1A, 5-HT1B, presynaptic sites), it can be considered a selective alkylating agent, since it exerted no action on 3H-spiperone binding to 5-HT2 sites, 3H-muscimol binding to GABA sites, or 3H-flunitrazepam binding to benzodiazepine sites.
authors.forename: M B
authors.initials: MB
authors.lastname: Emerit
authors.forename: H
authors.initials: H
authors.lastname: Gozlan
authors.forename: M D
authors.initials: MD
authors.lastname: Hall
authors.forename: M
authors.initials: M
authors.lastname: Hamon
authors.forename: A
authors.initials: A
authors.lastname: Marquet
mesh_terms: D015081:2-Naphthylamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D005033:Ethylmaleimide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000378:metabolism
chemical_list: D009281:Naphthalenes; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C044827:8-methoxy-2-(N-2'-chloropropyl-N-propyl)aminotetralin; D015081:2-Naphthylamine; D005033:Ethylmaleimide