The role of 5-HT1D and 5-HT1A receptors in mediating 5-hydroxytryptophan induced myoclonic jerks in guinea pigs
| Autor: | Jonathan P. Hatcher, Jim J. Hagan, Paula D. Slade |
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| Rok vydání: | 1995 |
| Předmět: |
Agonist
Male medicine.medical_specialty medicine.drug_class Pyridines Myoclonic Jerk Guinea Pigs Ritanserin Epilepsies Myoclonic CHO Cells Piperazines 5-Hydroxytryptophan Species Specificity Internal medicine Cricetinae medicine Animals Humans GR-127935 5-HT receptor Pharmacology 8-Hydroxy-2-(di-n-propylamino)tetralin Chemistry Receptor antagonist Rats Endocrinology Receptors Serotonin 5-HT1 receptor Serotonin Antagonists medicine.symptom Myoclonus medicine.drug |
| Zdroj: | European journal of pharmacology. 294(2-3) |
| ISSN: | 0014-2999 |
| Popis: | 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-HT 2A 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. |
| Databáze: | OpenAIRE |
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