Document Detail

Biochemical and behavioural effects of isamoltane, a beta-adrenoceptor antagonist with affinity for the 5-HT1B receptor of rat brain.
MedLine Citation:
PMID:  1674359     Owner:  NLM     Status:  MEDLINE    
The biochemical and behavioural effects of isamoltane, a beta-adrenoceptor and 5-HT1B receptor antagonist that has higher affinity for 5-HT1B receptors than for 5-HT1A receptors, on 5-HT neurotransmission in the rat brain were examined. In binding experiments isamoltane was found to be about five times more potent as a ligand for the 5-HT1B receptor than for the 5-HT1A receptor (Ki values 21 and 112 nmol/l, respectively). Isamoltane increased the K(+)-evoked overflow of 3H from 3H-5-HT loaded slices of rat occipital cortex at 0.1 mumol/l, consistent with inhibition of the terminal 5-HT autoreceptor. In vivo, isamoltane significantly increased the concentration of 5-hydroxyindoleacetic acid in hypothalamus and hippocampus indicating an increased 5-HT turnover with a maximal effect at 3 mg/kg s.c. A higher dose produced a less pronounced effect. This effect did not seem to be due to the beta-adrenoceptor blocking action of isamoltane since the beta-adrenoceptor antagonists. (-)-alprenolol, betaxolol or ICI 118.551 had no significant effects on 5-HT turnover at 5 mg/kg s.c. Isamoltane at 3 mg/kg s.c. induced the wet-dog shake response which was blocked by the tryptophan hydroxylase inhibitor p-chlorophenylalanine. In contrast, the same response induced by the 5-HT2 receptor agonist quipazine was not blocked by pretreatment with p-chlorophenylalanine. The wet-dog shakes evoked by isamoltane and quipazine were blocked by ritanserin, which indicates that 5-HT2 receptors are involved in their expression. These observations indicate that isamoltane, by inhibiting the terminal 5-HT autoreceptors, increased the synaptic concentration of 5-HT to a level that induced a behavioural response.
L Rényi; L G Larsson; S Berg; B E Svensson; G Thorell; S B Ross
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Naunyn-Schmiedeberg's archives of pharmacology     Volume:  343     ISSN:  0028-1298     ISO Abbreviation:  Naunyn Schmiedebergs Arch. Pharmacol.     Publication Date:  1991 Jan 
Date Detail:
Created Date:  1991-06-19     Completed Date:  1991-06-19     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  1-6     Citation Subset:  IM    
CNS 1, Astra Research Centre AB, Södertälje, Sweden.
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MeSH Terms
Adrenergic beta-Antagonists / pharmacology
Anti-Anxiety Agents / pharmacology*
Behavior, Animal / drug effects
Brain / metabolism*,  ultrastructure
Cerebral Cortex
Potassium / pharmacology
Propanolamines / pharmacology*
Rats, Inbred Strains
Receptors, Serotonin / metabolism*
Serotonin / physiology
Synaptic Transmission / drug effects
Tritium / diagnostic use
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Anti-Anxiety Agents; 0/Propanolamines; 0/Receptors, Serotonin; 10028-17-8/Tritium; 50-67-9/Serotonin; 7440-09-7/Potassium; 99740-06-4/isamoltane

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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