HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Effects of single and repeated administration of 1,2,3,4-tetrahydroisoquinoline analogs on the binding of [11C]raclopride to dopamine D2 receptors in the mouse brain.

Abstract
We investigated the effects of intraperitoneal injection of 1,2,3,4-tetrahydroisoquinoline (TIQ) analogs and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the binding of [11C]raclopride to striatal dopamine D2 receptors in mice. The binding of [11C]raclopride, but not of [11C]N-methylspiperone or [11C]nemonapride with higher affinity, to the receptors was significantly decreased immediately after TIQ injection. Neither a dopamine transporter blocker induced such effect nor TIQ affected the dopamine transporter-radioligand binding. Among the compounds investigated, including parkinsonism-inducing TIQ and (R/S)-1-benzyl-TIQ, parkinsonism-preventing (R)- and (S)-1-methyl-TIQ, and probable N-methylated metabolites of TIQ and 1-methyl-TIQ, TIQ and (S)-1-methyl-TIQ had the strongest effect on the binding of [11C]raclopride, and N-methylated derivatives showed less of an effect than the respective parent compounds. The decrease in the binding of [11C]raclopride continued for 7 hours and was followed by an increase until 10 days after the single and subchronic administration of TIQ. These findings suggest that TIQ analogs profoundly stimulated dopamine release which resulted in the competitive inhibition of the binding of [11C]raclopride to dopamine D2 receptors, but did not induce degeneration of the receptors.
AuthorsK Ishiwata, Y Koyanagi, T Saitoh, K Taguchi, J Toda, T Sano, M Senda
JournalJournal of neural transmission (Vienna, Austria : 1996) (J Neural Transm (Vienna)) Vol. 108 Issue 10 Pg. 1111-25 ( 2001) ISSN: 0300-9564 [Print] Austria
PMID11725814 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Carbon Radioisotopes
  • Dopamine Antagonists
  • Isoquinolines
  • Neurotoxins
  • Receptors, Dopamine D2
  • Tetrahydroisoquinolines
  • Raclopride
  • 1,2,3,4-tetrahydroisoquinoline
Topics
  • Animals
  • Brain (drug effects, metabolism)
  • Carbon Radioisotopes (administration & dosage)
  • Dopamine Antagonists (metabolism)
  • Dose-Response Relationship, Drug
  • Injections, Intraperitoneal
  • Injections, Intravenous
  • Isoquinolines (administration & dosage, chemistry)
  • Male
  • Mice
  • Neurotoxins (administration & dosage, chemistry)
  • Raclopride (metabolism)
  • Receptors, Dopamine D2 (metabolism)
  • Tetrahydroisoquinolines

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: