title: Assessment of mechanisms involved in antinociception produced by the alkaloid caulerpine.
abstract: In previous works we showed that oral administration of caulerpine, a bisindole alkaloid isolated from algae of the genus Caulerpa, produced antinociception when assessed in chemical and thermal models of nociception. In this study, we evaluated the possible mechanism of action of this alkaloid in mice, using the writhing test. The antinociceptive effect of caulerpine was not affected by intraperitoneal (i.p.) pretreatment of mice with naloxone, flumazenil, l-arginine or atropine, thus discounting the involvement of the opioid, GABAergic, l-arginine-nitric oxide and (muscarinic) cholinergic pathways, respectively. In contrast, i.p. pretreatment with yohimbine, an α2-adrenoceptor antagonist, or tropisetron, a 5-HT3 antagonist, significantly blocked caulerpine-induced antinociception. These results suggest that caulerpine exerts its antinociceptive effect in the writhing test via pathways involving α2-adrenoceptors and 5-HT3 receptors. In summary, this alkaloid could be of interest in the development of new dual-action analgesic drugs.
authors.affiliation: Laboratory of Pharmacology and Immunity, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceió 57020-720, Brazil. luiz0710@gmail.com.
authors.forename: Luiz Henrique Agra
authors.initials: LH
authors.lastname: Cavalcante-Silva
authors.affiliation: Laboratory of Pharmacology and Immunity, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceió 57020-720, Brazil. falcao.map@outlook.com.
authors.forename: Maria Alice Pimentel
authors.initials: MA
authors.lastname: Falcão
authors.affiliation: Laboratory of Pharmacology and Immunity, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceió 57020-720, Brazil. carolinavieira2708@gmail.com.
authors.forename: Ana Carolina Santana
authors.initials: AC
authors.lastname: Vieira
authors.affiliation: Laboratory of Pharmacology and Immunity, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceió 57020-720, Brazil. viana.mdm@gmail.com.
authors.forename: Max Denisson Maurício
authors.initials: MD
authors.lastname: Viana
authors.affiliation: Laboratory of Medicinal Chemistry, Posgraduate Program in Pharmaceutical Sciences, Federal University of Alagoas, Maceió 57020-720, Brazil. jotaaraujo2004@gmail.com.
authors.forename: João Xavier
authors.initials: JX
authors.lastname: de Araújo-Júnior
authors.affiliation: Postgraduate Program in Natural Products and Synthetic Bioactive, Federal University of Paraíba, João Pessoa 58051-900, Brazil. jessicacelestino26@hotmail.com.
authors.forename: Jéssica Celestino Ferreira
authors.initials: JC
authors.lastname: Sousa
authors.affiliation: Molecular Sciences Department, Federal Rural University of Pernambuco, Recife 52171-900, Brazil. taniasarmento@dcm.ufrpe.br.
authors.forename: Tania Maria Sarmento
authors.initials: TM
authors.lastname: da Silva
authors.affiliation: Postgraduate Program in Natural Products and Synthetic Bioactive, Federal University of Paraíba, João Pessoa 58051-900, Brazil. jbarbosa@ltf.ufpb.br.
authors.forename: José Maria
authors.initials: JM
authors.lastname: Barbosa-Filho
authors.affiliation: Laboratory of Biochemical and Molecular Pharmacology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-912, Brazil. fnoel@pharma.ufrj.br.
authors.forename: François
authors.initials: F
authors.lastname: Noël
authors.affiliation: Laboratory of Marine Algae, Department of Systematics and Ecology, Federal University of Paraíba, João Pessoa 58051-900, Brazil. mirandag@dse.ufpb.br.
authors.forename: George Emmanuel C
authors.initials: GE
authors.lastname: de Miranda
authors.affiliation: Postgraduate Program in Natural Products and Synthetic Bioactive, Federal University of Paraíba, João Pessoa 58051-900, Brazil. barbara@ltf.ufpb.br.
authors.forename: Bárbara Viviana de Oliveira
authors.initials: BV
authors.lastname: Santos
authors.affiliation: Laboratory of Pharmacology and Immunity, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceió 57020-720, Brazil. suzana.magna@gmail.com.
authors.forename: Magna Suzana
authors.initials: MS
authors.lastname: Alexandre-Moreira
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage* / Q000737:chemistry; D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D009270:Naloxone / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism; D059226:Nociceptive Pain / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010147:Pain Measurement; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects / Q000378:metabolism; D000077526:Tropisetron; D015016:Yohimbine / Q000008:administration & dosage
chemical_list: D000470:Alkaloids; D000700:Analgesics; D007211:Indoles; D018341:Receptors, Adrenergic, alpha-2; D044406:Receptors, Serotonin, 5-HT3; C000392:caulerpin; D015016:Yohimbine; D009569:Nitric Oxide; D009270:Naloxone; D000077526:Tropisetron