title: D-16949 (anpirtoline): a novel serotonergic (5-HT1B) psychotherapeutic agent assessed by its discriminative effects in the rat.
abstract: D-16949 [6-chlor-2-(piperidyl-4-thio)-pyridine; Anpirtoline] is a novel centrally acting compound with serotonergic effects. To assess its discriminative stimulus effects, rats were trained to discriminate D-16949 (2.0 mg/kg i.p., 30 min) from no drug. D-16949 induced dose-dependent discriminative stimulus effects (ED50, 0.31 mg/kg), and did not produce sedation. The opioid analgesics codeine, pentazocine and tramadol all failed to substitute for D-16949. The opioid antagonist naltrexone did not antagonize the discriminative stimulus effects of D-16949. Phencyclidine, d-amphetamine, lysergic acid diethylamide and quipazine produced between 0 and 35% responding on the D-16949 lever. 8-Hydroxy-2-(di-n-propylamino)-tetralin substituted partially (45%) for D-16949, whereas 1-(m-trifluoromethylphenyl)-piperazine and RU 24969 completely and dose-dependently substituted for D-16949. The discriminative stimulus effects of D-16949 were not reversed by either cyproheptadine, ketanserin, pirenperone, spiperone or methylsergide. The 5-hydroxytryptamine3 (5-HT3) active antagonists ICS 205-930 and MDL 72222 were also ineffective as D-16949 antagonists. It is concluded that the discriminative stimulus effects of D-16949 are not mediated through opioid or 5-HT2 mechanisms. The present data also do not suggest the involvement of 5-HT3 mechanisms, but that D-16949 produces its discriminative stimulus effects in the rat primarily via agonistic actions at 5-HT1B receptors.
authors.affiliation: Department of Health and Human Services, National Institute of Drug Abuse, Baltimore, Maryland.
authors.forename: M D
authors.initials: MD
authors.lastname: Swedberg
authors.forename: H E
authors.initials: HE
authors.lastname: Shannon
authors.forename: B
authors.initials: B
authors.lastname: Nickel
authors.forename: S R
authors.initials: SR
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects*; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011957:Receptors, Opioid / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D010879:Piperazines; D010880:Piperidines; D011725:Pyridines; D011957:Receptors, Opioid; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C018406:1-(3-trifluoromethylphenyl)piperazine; C075631:anpirtoline; D003913:Dextroamphetamine