title: 22-azidosalvinorin A exhibits antidepressant-like effect in mice.
abstract: The increasing cases of depression has made the searches for new drugs and understanding of the underligning neurobiology of this psychiatric disorder a necessity. Here, we modified the structure of salvinorin A (a known halucinogen) and investigated antidepressant-like activity of its four derivatives; 22-methylsulfanylsalvinorin A(SA1), 2-O-cinnamoylsalvinorin B (CSB), 22-azidosalvinorin A (SA2), and 2-O-(4'-azidophenylsulfonyl)salvinorin B (SA3). Prior to behavioural tests (Irwin test, open field test - OFT, forced swimming test - FST and tail suspension test - TST), SA1 was prepared by reacting salvinorin B and methylthioacetic acid with 89% yield; CSB was obtained from the reaction of salvinorin B and cinnamic acid with 92% yield; SA2 was obtained from the reaction of salvinorin B and azidoacetic acid with 81% yield; and SA3 was prepared by reacting salvinorin B with 4-azidophenylsulfonyl chloride with 80% yield. Oral treatment of mice with these derivatives (1-1000mg/kg) did not elicit toxic sign or death. Unlike SA, SA1, CSB and SA3, treatment with SA2 (5, 10 and 20mg/kg) decreased the immobility (TST and FST) and swimming time (FST) without altering locomotor activity in OFT. A decrease in the immobility time in TST and FST confirmed antidepressant-like property of SA2. Although p-chlorophenylalanine (serotonin depletor) or WAY100635 (selective 5-HT1Areceptor antagonist) did not attenuate effect of SA2, alpha-methyl-para-tyrosine (catecholamine depletor) and prazosin (selective α1-receptor antagonist) attenuated this effect. SA2 mildly inhibited monoamine oxidase and showed affinity for α1A, α1B, α1D and κ-opioid receptor subtypes. In summary, SA2 induced monoamine-mediated antidepressant-like effect.
authors.affiliation: Department of Pharmacology, Federal University of Goias, Campus Samambaia, 74001-970 Goiania, GO, Brazil; Center for Studies and Toxicological-Pharmacological Research, Faculty of Pharmacy, Federal University of Goiás, PMB 131, CEP 74001-970, Goiânia, Brazil. Electronic address: olulolo@yahoo.com.
authors.forename: James Oluwagbamigbe
authors.initials: JO
authors.lastname: Fajemiroye
authors.affiliation: Department of BioMolecular Sciences, Division of Pharmacognosy, School of Pharmacy, University of Mississippi, P.O. Box 1848, MS 38677, USA.
authors.forename: Polepally Reddy
authors.initials: PR
authors.lastname: Prabhakar
authors.affiliation: Center for Studies and Toxicological-Pharmacological Research, Faculty of Pharmacy, Federal University of Goiás, PMB 131, CEP 74001-970, Goiânia, Brazil.
authors.forename: Luiz Carlos da
authors.initials: LC
authors.lastname: Cunha
authors.affiliation: Department of Pharmacology, Federal University of Goias, Campus Samambaia, 74001-970 Goiania, GO, Brazil.
authors.forename: Elson Alves
authors.initials: EA
authors.lastname: Costa
authors.affiliation: Department of BioMolecular Sciences, Division of Pharmacognosy, School of Pharmacy, University of Mississippi, P.O. Box 1848, MS 38677, USA.
authors.forename: Jordan K
authors.initials: JK
authors.lastname: Zjawiony
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001386:Azides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D045785:Diterpenes, Clerodane / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D013550:Swimming
chemical_list: C000617591:22-azidosalvinorin A; D000928:Antidepressive Agents; D001386:Azides; D045785:Diterpenes, Clerodane; D011957:Receptors, Opioid; D008995:Monoamine Oxidase; C090499:salvinorin A
keywords: 22-azidosalvinorin A; Adrenoceptors; Depression; Monoamines; Salvinorin A; κ-opioid receptor