Abstract | RATIONALE: OBJECTIVE: MATERIALS AND METHODS: RESULTS: In C57BL/6J mice, GHB, the GHB precursor gamma-butyrolactone (GBL), and the GABA(B) receptor agonists baclofen and SKF97541 all produced catalepsy but differed in potency (i.e., SKF97541> baclofen>GBL>GHB) and in onset of action. The cataleptic effects of drug combinations were assessed at the time of peak effect of each compound, i.e., 60 min after CGP35348 and 60, 30, 30, and 15 min after baclofen, SKF97541, GHB, and GBL, respectively. At 100 mg/kg, CGP35348 shifted the dose-response curves of baclofen and SKF97541 to the right but not those of GHB and GBL; at 320 mg/kg, CGP35348 shifted the curves of all four compounds to the right. CONCLUSIONS: The finding that CGP35348 was about threefold less potent to antagonize GHB and GBL than baclofen and SKF97541 is further evidence that the mechanisms mediating the effects of GHB and GABA(B) agonists are not identical. Differential involvement of GABA(B) receptor subtypes, or differential interactions with GABA(B) receptors, may possibly explain why GHB is effective for treating narcolepsy and is abused whereas baclofen is not.
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Authors | Wouter Koek, Susan L Mercer, Andrew Coop |
Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 192
Issue 3
Pg. 407-14
(Jun 2007)
ISSN: 0033-3158 [Print] Germany |
PMID | 17277933
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- GABA Agonists
- GABA Antagonists
- GABA-B Receptor Agonists
- Organophosphorus Compounds
- Receptors, GABA-B
- 3-aminopropyl(methyl)phosphinic acid
- Sodium Oxybate
- CGP 35348
- Baclofen
- 4-Butyrolactone
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Topics |
- 4-Butyrolactone
(administration & dosage, pharmacology)
- Animals
- Baclofen
(administration & dosage, pharmacology)
- Catalepsy
(chemically induced)
- Dose-Response Relationship, Drug
- GABA Agonists
(administration & dosage, pharmacology)
- GABA Antagonists
(administration & dosage, pharmacology)
- GABA-B Receptor Agonists
- Male
- Mice
- Mice, Inbred C57BL
- Narcolepsy
(drug therapy)
- Organophosphorus Compounds
(administration & dosage, pharmacology)
- Receptors, GABA-B
(drug effects)
- Sodium Oxybate
(administration & dosage, pharmacology)
- Substance-Related Disorders
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