Locomotor inhibition, yawning and vacuous chewing induced by a novel dopamine D2 post-synaptic receptor agonist

Eur J Pharmacol. 1997 Mar 26;323(1):27-36. doi: 10.1016/s0014-2999(97)00026-5.


The N-n-propyl analog of dihydrexidine ((+/-)-trans-10, 11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine) is a dopamine receptor agonist with high affinity for dopamine D2 and D3 receptors (K0.5 = 26 and 5 nM, respectively). Members of the hexahydrobenzo[a]phenanthridine structural class are atypical because they display high intrinsic activity at post-synaptic dopamine D2 receptors, but low intrinsic activity at dopamine D2 autoreceptors. The present study examined the effects of (+/-)-N-n-propyl-dihydrexidine on unconditioned behaviors in rats. The most striking results observed were large, dose-dependent decreases in locomotor activity (e.g., locomotor inhibition), and increases in vacuous chewing; yawning was also increased at the highest dose of (+/-)-N-n-propyl-dihydrexidine. The locomotor inhibition and yawning induced by (+/-)-N-n-propyl-dihydrexidine were blocked by pre-treatment with (-)-remoxipride (S(-)-3-bromo-N-((1-ethyl-2-pyrrolidinyl)-methyl)-2, 6-dimethoxybenzamide), a dopamine D2 receptor antagonist, but not by the dopamine D1 receptor antagonist (+)-SCH23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine). Vacuous chewing was decreased by both (-)-remoxipride and (+)-SCH23390. These data support the hypothesis that a subpopulation of post-synaptic dopamine D2 receptors has a critical role in decreases in locomotor activity and induction of vacuous chewing and yawning.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic alpha-2 Receptor Antagonists
  • Adrenergic alpha-Antagonists / pharmacology
  • Analysis of Variance
  • Animals
  • Apomorphine / administration & dosage
  • Apomorphine / pharmacology
  • Benzazepines / administration & dosage
  • Benzazepines / pharmacology
  • Computer Simulation
  • Dopamine Agonists / pharmacology*
  • Dopamine Antagonists / administration & dosage
  • Dopamine Antagonists / pharmacology
  • Dopamine D2 Receptor Antagonists
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Idazoxan / pharmacology
  • Locomotion / drug effects*
  • Male
  • Mastication / drug effects*
  • Phenanthridines / chemistry
  • Phenanthridines / metabolism
  • Phenanthridines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D2 / agonists*
  • Receptors, Dopamine D3
  • Reference Standards
  • Remoxipride / administration & dosage
  • Remoxipride / pharmacology
  • Stereoisomerism
  • Yawning / drug effects*


  • Adrenergic alpha-2 Receptor Antagonists
  • Adrenergic alpha-Antagonists
  • Benzazepines
  • Dopamine Agonists
  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Drd3 protein, rat
  • Phenanthridines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Remoxipride
  • dihydrexidine
  • Apomorphine
  • Idazoxan