Abstract |
The capacity of the putative S2 serotonin receptor antagonists, pirenperone, pipamperone, ketanserin and cinanserin, to block the myoclonic syndrome produced by 30 mg/kg of L-5-hydroxytryptophan (5-HTP) [after lesioning 5-hydroxytryptamine (serotonin, 5-HT)-containing neurons with 5,7-dihydroxytryptamine (DHT)] or 15 mg/kg of fenfluramine (FF) or p-chloroamphetamine (PCA) was tested in adult male Sprague-Dawley rats. S2 antagonists inhibited limb (arrhythmic and asynchronous) and axial (truncal) myoclonus in a dose-dependent manner in the rank order of potency: pirenperone greater than pipamperone greater than ketanserin = cinanserin. Abnormal movements ( myoclonus, lateral head weaving) of the myoclonic syndromes were better antagonized than postural abnormalities (hindlimb abduction, hunching of back). Centrally acting drugs, selective for S2 receptors ( pirenperone, pipamperone), exhibited greater antimyoclonic properties than the non-selective 5-HT antagonist methysergide, which was as effective as ketanserin and cinanserin. Significant non-specific reduction in myoclonus without the improvement of other behavioral responses followed treatment with sedative/ neuroleptic drugs, such as haloperidol (but not the non- neuroleptic dopamine antagonist sulpiride), clonazepam and diazepam. The anticonvulsants valproic acid (100 and 300 mg/kg), adrenocorticotrophic hormone ( ACTH; 100 and 300 U/kg), diphenylhydantoin (15 mg/kg), and phenobarbital (20 mg/kg) and drugs which do not act principally at S2 receptors were ineffective in these models. These data support the hypothesis that myoclonus in behavioral models induced by 5-HT is S2 receptor mediated. S2 antagonists could have a role in the treatment of human myoclonus.
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Authors | M R Pranzatelli, S R Snodgrass |
Journal | Neuropharmacology
(Neuropharmacology)
Vol. 25
Issue 1
Pg. 5-12
(Jan 1986)
ISSN: 0028-3908 [Print] England |
PMID | 2936977
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Butyrophenones
- Piperidines
- Receptors, Serotonin
- Serotonin Antagonists
- pipamperone
- Ketanserin
- 5-Hydroxytryptophan
- Cinanserin
- pirenperone
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Topics |
- 5-Hydroxytryptophan
- Animals
- Brain Chemistry
- Butyrophenones
(therapeutic use)
- Cinanserin
(therapeutic use)
- Ketanserin
- Male
- Myoclonus
(chemically induced, drug therapy, metabolism)
- Piperidines
(therapeutic use)
- Rats
- Rats, Inbred Strains
- Receptors, Serotonin
(analysis)
- Serotonin Antagonists
(therapeutic use)
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