Synthesis and Trazodone-like Analgesic Activity of 4-Phenyl-6-aryl-2-[3-(4-arylpiperazin-1-yl)propyl]pyridazin-3-ones

スポンサーリンク

概要

• 論文の詳細を見る

• A series of 4,6-diaryl pyridazinones, chemically related to trazodone, was synthesized and evaluated for analgesic activity. With ED_<50> values ranging from 8.4 to 46.7 mg kg^<-1> i.p. in the phenylbenzoquinone-induced writhing test (PBQ test), most compounds were several times more potent than acetaminophen (ED_<50>=231.3 mg kg^<-1> i.p.) and noramidopyrine (ED_<50>=68.5 mg kg^<-1> i.p.). A multiple linear regression analysis demonstrated a correlation between antinociceptive activity and lipophilicity, as well as electronic and steric factors. The most active pyridazinones 2c and 2j exhibited minimal sedative and neurotoxic effects at the dose of 25 mg kg^<-1> i.p. They were devoid of activity in the hot plate test and their analgesic activity was not significantly reversed by naloxone in the PBQ test. The antinociceptive response induced by morphine (0.15 mg kg^<-1> s.c.) in the PBQ test was greatly potentiated by 2c and 2j administered at the low doses of 1 and 2.5 mg kg^<-1> i.p., respectively. On the other hand, their analgesic effects were enhanced synergistically by 5-hydroxytryptophan combined with carbidopa. All these data imply that a significant part of the antinociceptive effect induced by 2c and 2j may involve both opioid and serotenergic pathways. In addition, these two pyridazinones did not exhibit any antidepressant properties in the forced swimming test, nor did they potentiate yohimbine-induced toxicity.

• 公益社団法人日本薬学会の論文
• 1996-05-15

著者

• Couquelet J

  Groupe De Recherche En Pharmacochimie Laboratoire De Chimie Therapeutique Faculte Des Sciences Pharm

• COUDERT Pascal

  Groupe de Recherche en Pharmacochimie, Laboratoire de Chimie Therapeutique Faculte des Sciences Phar

• RUBAT Catherine

  Laboratoire de Pharmacologie Faculte des Sciences Pharmaceutiques, Universite Francois Rabelais

• ALBUISSON Eliane

  Laboratoire de Biomathematiques et Informatique Medicale

• COUQUELET Jacques

  Groupe de Recherche en Pharmacochimie, Laboratoire de Chimie Therapeutique Faculte des Sciences Phar

• ROHET Florence

  Groupe de Recherche en Pharmacochimie, Laboratoire de Chimie Therapeutique

• Rohet Florence

  Groupe De Recherche En Pharmacochimie Laboratoire De Chimie Therapeutique

• Coudert Pascal

  Groupe De Recherche En Pharmacochimie Laboratoire De Chimie Therapeutique Faculte Des Sciences Pharm

• Rubat C

  Laboratoire De Pharmacologie Faculte Des Sciences Pharmaceutiques Universite Francois Rabelais

• Couquelet Jacques

  Groupe De Recherche En Pharmacochimie Faculte De Pharmacie

関連論文

• Synthesis and Pharmacological Evaluation in Mice of New Non-classical Antinociceptive Agents, 5-(4-Arylpiperazin-1-yl)-4-benzyl-1,2-oxazin-6-ones
• Synthesis and Trazodone-like Analgesic Activity of 4-Phenyl-6-aryl-2-[3-(4-arylpiperazin-1-yl)propyl]pyridazin-3-ones
• Effect on Free Radical Processes of Some Ascorbic Acid Analogues
• Synthesis and Aldose Reductase Inhibitory Activity of Triazine Derivatives Possessing Acetic Acid Group
• Synthesis and Analgesic Effect of N-Substituted 5-Arylidene-6-methyl-3-(4H)-pyridazinones
• Immunomodulatory Agents : Dioxothiadiazabicyclo[3.3.0]octanes and Their 2-Spiro Derivatives
• Anticonvulsant Activity of 3-Oxo-5-substituted Benzylidene-6-methyl-(4H)-2-pyridazinylacetamides and 2-Pyridazinylacetylhydrazides
• Synthesis and Pharmacological Evaluation of N-Substituted 4,6-Diaryl-3-pyridazinones as Analgesic, Antiinflammatory and Antipyretic Agents
• Antidepressant Activity of New 3-Amino-5-disubstituted Benzylidene-6-methyl-(4H)-pyridazine Derivatives

スポンサーリンク