3-aminopyridazine derivatives with atypical antidepressant, serotonergic, and dopaminergic activities

J Med Chem. 1989 Mar;32(3):528-37. doi: 10.1021/jm00123a004.

Abstract

Minaprine [3-[(beta-morpholinoethyl)amino]-4-methyl-6-phenylpyridazine dihydrochloride] is active in most animal models of depression and exhibits in vivo a dual dopaminomimetic and serotoninomimetic activity profile. In an attempt to dissociate these two effects and to characterize the responsible structural requirements, a series of 47 diversely substituted analogues of minaprine were synthesized and tested for their potential antidepressant, serotonergic, and dopaminergic activities. The structure-activity relationships show that dopaminergic and serotonergic activities can be dissociated. Serotonergic activity appears to be correlated mainly with the substituent in the 4-position of the pyridazine ring whereas the dopaminergic activity appears to be dependent on the presence, or in the formation, of a para-hydroxylated aryl ring in the 6-position of the pyridazine ring.

MeSH terms

  • Animals
  • Antidepressive Agents / chemical synthesis*
  • Chemical Phenomena
  • Chemistry
  • Dopamine Agents / chemical synthesis*
  • Female
  • Mice
  • Pyridazines / chemical synthesis*
  • Pyridazines / pharmacology
  • Receptors, Dopamine / drug effects
  • Receptors, Serotonin / drug effects*
  • Structure-Activity Relationship

Substances

  • Antidepressive Agents
  • Dopamine Agents
  • Pyridazines
  • Receptors, Dopamine
  • Receptors, Serotonin
  • minaprine