Document Detail

Central and peripheral injections of the 5-HT2 agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, modify cardiovascular function through different mechanisms.
MedLine Citation:
PMID:  1762059     Owner:  NLM     Status:  MEDLINE    
The mechanisms underlying the cardiovascular effects of central and peripheral administration of the 5-HT2 (serotonin) receptor agonist (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) were studied in conscious rats. Intravenous (10-1000 nmol/kg) and i.c.v. (3-300 nmol) administration of DOI produced dose-related elevations of arterial pressure without altering heart rate except after injection of the highest doses. Pretreatment with xylamidine tosylate, a 5-HT2 receptor antagonist that does not cross the blood-brain barrier, blocked the pressor response to i.v., but not i.c.v., administration of equivalent doses of DOI. Pretreatment with the vasopressin receptor antagonist d(CH2)5Tyr(Me)AVP significantly reduced the pressor response to i.c.v., but not i.v., administration of DOI. Prior ganglionic blockade with chlorisondamine amplified the pressor response to both i.v. and i.c.v. administration of DOI. Pretreatment with a combination of chlorisondamine, xylamidine and d(CH2)5Tyr(Me)AVP abolished the pressor response to i.c.v. administration of DOI. Thus, the pressor response to i.v. administration of DOI was mediated at sites outside the blood-brain barrier, most likely at vascular 5-HT2 receptors, and was not secondary to vasopressin release. Inappropriate heart rate changes attended the pressor responses to i.v. administration of DOI, suggesting an action at extravascular sites. The pressor response to i.c.v. administration of DOI resulted from a combination of vasopressin release, modulation of autonomic nervous outflow and some leakage into the periphery.
A Dedeoğlu; L A Fisher
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  259     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1991 Dec 
Date Detail:
Created Date:  1992-02-07     Completed Date:  1992-02-07     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1027-34     Citation Subset:  IM    
Department of Pharmacology, University of Arizona College of Medicine, Tucson.
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MeSH Terms
Amidines / pharmacology
Amphetamines / pharmacology*
Arginine Vasopressin / analogs & derivatives,  pharmacology
Behavior, Animal / drug effects
Blood Pressure / drug effects
Cardiovascular Physiological Phenomena
Cardiovascular System / drug effects*
Chlorisondamine / pharmacology
Dose-Response Relationship, Drug
Injections, Intravenous
Injections, Intraventricular
Locomotion / drug effects
Rats, Inbred Strains
Serotonin / physiology*
Serotonin Antagonists / pharmacology*
Reg. No./Substance:
0/Amidines; 0/Amphetamines; 0/Serotonin Antagonists; 113-79-1/Arginine Vasopressin; 50-67-9/Serotonin; 6443-50-1/xylamidine; 64584-34-5/4-iodo-2,5-dimethoxyphenylisopropylamine; 73168-24-8/vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; 7701-62-4/Chlorisondamine

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

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