The role of 5-HT1D and 5-HT1A receptors in mediating 5-hydroxytryptophan induced myoclonic jerks in guinea pigs.

Abstract

Systemic administration of 5-hydroxytryptophan (5-HTP) to guinea pigs causes species-specific, rhythmic, whole body jerks (myoclonic jerks), the frequency and amplitude of which were measured in an automated apparatus. The brain penetrant 5-HT1D receptor agonist 3-(2-dimethylaminoethyl)-4-chloro-5-propoxyindole hemifumarate (SKF 99101H) (3-30 mg/kg i.p.) and the selective 5-HT1A receptor agonist (+/-)8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.3-3 mg/kg s.c.) dose dependently potentiated the frequency and intensity of myoclonic jerks caused by 5-HTP (100 mg/kg). Cotreatment of guinea pigs with 8-OH-DPAT (3 mg/kg s.c.) and SKF 99101H (30 mg/kg i.p.), which were inactive when given alone, gave a marked myoclonic jerk response. Conversely, the myoclonic jerk response to higher doses of 5-HTP (150 mg/kg i.p.) was dose dependently blocked by the 5-HT1D receptor antagonist GR 127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1 ,2,4-oxadiazol-3-yl)[1,1'-biphenyl]4-carboxamide oxalate) (ED50 0.32 mg/kg i.p.) and the selective 5-HT1A receptor antagonist WAY 100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride) (ED50 0.33 mg/kg i.p.). The response to 5-HTP (150 mg/kg i.p.) was also blocked by ritanserin (0.01-0.3 mg/kg i.p.). Our data therefore confirm previous reports concerning the effects of 5-HT2A/2C receptor blockade on 5-HTP induced myoclonic jerks and suggest that both 5-HT1D and 5-HT1A receptors play an important role in mediating this behavioural response.

• Authors: J J Hagan, J P Hatcher, P D Slade
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 294 Issue 2-3 Pg. 743-51 (Dec 29 1995) ISSN: 0014-2999 [Print] Netherlands
• PMID: 8750741 (Publication Type: Journal Article)

Chemical References

• Piperazines
• Pyridines
• Receptors, Serotonin
• Serotonin Antagonists
• N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
• 8-Hydroxy-2-(di-n-propylamino)tetralin
• 5-Hydroxytryptophan

Topics

• 5-Hydroxytryptophan (toxicity)
• 8-Hydroxy-2-(di-n-propylamino)tetralin (pharmacology)
• Animals
• CHO Cells
• Cricetinae
• Epilepsies, Myoclonic (chemically induced)
• Guinea Pigs
• Humans
• Male
• Piperazines (pharmacology)
• Pyridines (pharmacology)
• Rats
• Receptors, Serotonin (physiology)
• Serotonin Antagonists (pharmacology)
• Species Specificity