Pre- and postsynaptic effects of SKF64139, a phenylethanolamine N-methyltransferase inhibitor, in conscious normotensive rats

Details

Serval ID
serval:BIB_C33E670EB7D1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Pre- and postsynaptic effects of SKF64139, a phenylethanolamine N-methyltransferase inhibitor, in conscious normotensive rats
Journal
Journal of Cardiovascular Pharmacology
Author(s)
Waeber B., Brunner  H. R., Haeusler G., Gavras H.
ISSN
0160-2446
Publication state
Published
Issued date
1982
Peer-reviewed
Oui
Volume
4
Number
5
Pages
759-64
Language
english
Notes
Journal Article
Research Support, Non-U.S. Gov't
Abstract
We investigated in conscious normotensive rats the effect of SKF64139 (2 mg i.v.), a potent phenylethanolamine N-methyltransferase (PNMT) inhibitor, on blood pressure responses to norepinephrine (40, 80, and 160 ng i.v.); methoxamine (2.5, 5 and 10 micrograms i.v.), a directly active sympathomimetic agent that is not taken up by adrenergic nerves; and tyramine (20, 40, and 80 micrograms i.v.), an indirectly acting sympathomimetic amine. The pressor effect of norepinephrine was not changed by 2 mg of SKF64139, while those of methoxamine and tyramine were significantly reduced. The dose-response curve to exogenous norepinephrine was also evaluated following blockade of norepinephrine uptake in the nerve endings using 0.25 mg desipramine i.v. This dose of desipramine had no effect on blood pressure increase induced by methoxamine. In rats pretreated with the neuronal uptake inhibitor desipramine in a dose that did not affect alpha-adrenoceptors, SKF64139 significantly decreased the pressor responses to norepinephrine. Increasing the dose of SKF64139 to 8 mg i.v. resulted in a significant fall in base-line blood pressure and in a blunted blood pressure response to norepinephrine. These data demonstrate that in vivo the PNMT inhibitor SKF64139 blocks alpha-adrenoceptors and inhibits neuronal uptake. The alpha-adrenoceptor blocking properties of SKF65139 are masked by simultaneous blockade of norepinephrine uptake when agonists with affinity for the uptake system are used. These findings need to be taken into account when interpreting cardiovascular effects of the PNMT inhibitor SKF64139.
Keywords
AnimalsBlood Pressure/*drug effectsDesipramine/pharmacologyDose-Response Relationship, DrugIsoquinolines/*pharmacologyMaleMethoxamine/pharmacologyNorepinephrine/pharmacologyPhenylethanolamine N-Methyltransferase/*antagonists & inhibitorsRatsRats, Inbred Strains*TetrahydroisoquinolinesTyramine/pharmacology
Pubmed
Web of science
Create date
04/03/2009 15:05
Last modification date
20/08/2019 15:38
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