title: Inactivation of D1 and D2 dopamine receptors by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in vivo: selective protection by neuroleptics.
abstract: Treatment of rats with the peptide coupling agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (6 mg/kg i.p.) irreversibly reduced the binding of [3H]spiperone ([3H]SPIP) and cis-[3H] piflutixol to striatal D2 and D1 receptors, respectively, by 70 to 75%. In each instance only the receptor density was affected, without a change in the dissociation constant (Kd) of either radioligand. Pretreatment with sulpiride (200 mg/kg i.p.), a selective D2 antagonist, preferentially protected [3H]SPIP sites against N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline-induced inactivation, whereas pretreatment with SCH 23390 (3 mg/kg i.p.), a putative selective D1 antagonist, preferentially blocked the inactivation of cis-[3H]piflutixol binding sites. N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline markedly reduced radioligand binding to cortical alpha-1 ([3H]prazosin) and alpha-2 [( 3H]yohimbine) receptors (10-20% of control) but had a lesser effect on serotonin-2 ([3H]SPIP) and serotonin-1 ([3H]5-HT) receptors (30-40% of control). Muscarinic cholinergic ([3H] quinuclidinyl benzilate) and beta adrenergic ([3H]dihydroalprenolol) receptors were only slightly affected. None of these nondopaminergic sites were protected by sulpiride or SCH 23390, with the exception of serotonin-2 and serotonin-1 which were partially protected by the latter. SPIP (0.2 mg/kg i.p.), haloperidol (1 mg/kg i.p.) and pimozide (2 mg/kg i.p.) all selectively protected the D2 receptor, whereas cis-flupenthixol (2 mg/kg i.p.) protected both dopamine receptors; its inactive isomer trans-flupenthixol (20 mg/kg i.p.) protected neither. Bulbocapnine (25 mg/kg s.c.) selectively, but partially, protected the D1 site.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.forename: E
authors.initials: E
authors.lastname: Meller
authors.forename: K
authors.initials: K
authors.lastname: Bohmaker
authors.forename: M
authors.initials: M
authors.lastname: Goldstein
authors.forename: A J
authors.initials: AJ
authors.lastname: Friedhoff
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects; D018492:Dopamine Antagonists; D066298:In Vitro Techniques; D008297:Male; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000317:Adrenergic alpha-Antagonists; D014150:Antipsychotic Agents; D001552:Benzazepines; D018492:Dopamine Antagonists; D011804:Quinolines; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; C000470:EEDQ