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Pharmaceutisch Weekblad

, Volume 4, Issue 5, pp 145–153 | Cite as

Pharmacodynamic effects and possible therapeutic uses of THIP, a specific GABA-agonist

  • A. V. Christensen
  • O. Svendsen
  • P. Krogsgaard-Larsen
Medicinal Chemistry Congress

Abstract

thip (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) is a potent and specificgaba receptor agonist which does not influence thegaba uptake system orgaba metabolizing enzymes. The specificity for thegaba receptor is also demonstrated by lack of action on monoaminergic, cholinergic, histaminergic or opiate receptors.

Since in recent yearsgaba receptor stimulants — among othersthip — have become available many have speculated as to what clinical indicationgaba-ergic stimulation might be an important element. The first suggestion was thatgaba-ergic drugs by an inhibitory effect on the dopamine neurons would improve the antischizophrenic effect of neuroleptics and improve tardive dyskinesia. Furthermore, studies on brains of deceased Parkinson and Huntington's chorea patients have demonstrated a low level ofgaba and its synthesizing enzyme glutamic acid decarboxylase (gad) in the basal ganglia. Also in epilepsy and diseases with dementia a deficit in thegaba system has been proposed. Therefore a therapeutic strategy for these diseases may be supplementary treatment with drugs which increasegaba receptor activity.

Furthermore, recent results in humans have shown thatgaba agonists perhaps also could be of benefit in mania and depressions. When considering the neurophysiological elements of nociception and muscle tone it is also reasonable to suggest thatgaba-ergic stimulation may reduce pain perception and muscle tone.

Keywords

Dopamine Dementia Glutamic Acid Muscle Tone Tardive Dyskinesia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1982

Authors and Affiliations

  • A. V. Christensen
    • 1
  • O. Svendsen
    • 1
  • P. Krogsgaard-Larsen
    • 2
  1. 1.Department of Pharmacology and ToxicologyH. Lundbeck & Co. A/SValbyDenmark
  2. 2.Department of Chemistry BCRoyal Danish School of PharmacyCopenhagen Ø.Denmark

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