Document Detail

The oral antihypertensive activity of the methylated derivatives of phenyl-2-aminoethyl sulfide.
MedLine Citation:
PMID:  8509996     Owner:  NLM     Status:  MEDLINE    
We have reported previously that phenyl-2-aminoethyl sulfide and its derivatives are excellent substrates for dopamine-beta-monooxygenase and produce an antihypertensive effect in spontaneously hypertensive rats after i.p. administration. In the studies reported herein, we demonstrate that alpha-methyl-phenyl-2-aminoethyl sulfide and 4-hydroxy-alpha-methyl-phenyl-2-aminoethyl sulfide, the methylated and hydroxymethylated derivatives of phenyl-2-aminoethyl sulfide, respectively, decrease mean arterial pressure in conscious, unrestrained spontaneously hypertensive rats after p.o. administration. This antihypertensive effect after p.o. administration occurs without the undesirable transient rise in blood pressure observed previously after i.p. administration. Results using the methodology of food-reinforced operant conditioned behavior are consistent with the interpretation that the ring hydroxylated derivatives, 4-hydroxy-phenyl-2-aminoethyl sulfide and 4-hydroxy-alpha-methyl-phenyl-2-aminoethyl sulfide, do not penetrate into the central nervous system. This finding supports our contention that the primary site of action for the antihypertensive activity of the sulfides may be the peripheral adrenergic nerve ending. In view of the current high degree of interest in chiral development, the enantiomeric specificity of the antihypertensive activity of alpha-methyl-phenyl-2-aminoethyl sulfide was also evaluated. Results from these studies demonstrate that the (S)-enantiomer of alpha-methyl-phenyl-2-aminoethyl sulfide is more effective in lowering blood pressure after p.o. administration than the (R)-enantiomer. The implications of our findings in terms of the mechanism of action of these compounds are discussed.
S H Pollock; M I Reichbaum; J C Colbert; P A Husain; J M Holbrook; A A Ogonowski; J S Khlief; S W May
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  265     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1993 Jun 
Date Detail:
Created Date:  1993-07-14     Completed Date:  1993-07-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1113-7     Citation Subset:  IM    
School of Pharmacy, Mercer University, Atlanta, Georgia.
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MeSH Terms
Administration, Oral
Antihypertensive Agents / administration & dosage,  pharmacology*
Conditioning, Operant
Phenols / administration & dosage,  pharmacology*
Propylamines / administration & dosage,  pharmacology*
Rats, Inbred SHR
Rats, Inbred WKY
Rats, Sprague-Dawley
Sulfides / administration & dosage,  pharmacology*
Grant Support
Reg. No./Substance:
0/Antihypertensive Agents; 0/Phenols; 0/Propylamines; 0/Sulfides; 115044-39-8/4-hydroxy-alpha-methylphenyl-2-aminoethylsulfide; 2014-77-9/1-(phenylthio)-2-aminopropane

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