Adenosine Analogs: Structure-Activity Relationships in Vascular and Intestinal Smooth Muscle

• Published in: Journal of pharmaceutical sciences 1973-09, Vol.62 (9), p.1449-1452
• Main Authors: Leslie, S.W., Borowitz, J.L., Miya, T.S.
• Format: Article
• Language: English
• Subjects: Adenosine - pharmacology; Adenosine analogs; Adenosine analogs, structure-activity relationships— relaxant effects on isolated ileal and aortic smooth muscle, blood pressure depression compared in guinea pig and dog; Animals; Aorta, Thoracic - drug effects; Blood Pressure - drug effects; blood pressure depression compared in guinea pig and dog; Blood pressure depression-adenosine analogs; Blood pressure depression—adenosine analogs, guinea pig and dog; Chromomycins - pharmacology; Dogs; Dose-Response Relationship, Drug; guinea pig and dog; Guinea Pigs; Ileum - drug effects; In Vitro Techniques; isolated ileal and aortic muscle-effects of adenosine analogs; Male; Muscle, Smooth - drug effects; Nicotine - pharmacology; Norepinephrine - pharmacology; Relaxation of isolated ileal and aortic smooth muscle-effects of adenosine analogs; Relaxation of isolated ileal and aortic smooth muscle—effects of adenosine analogs, structure-activity relationships; Smooth muscle relaxation; smooth muscle relaxation and blood pressure depression; Smooth muscle relaxation, isolated ileal and aortic muscle—effects of adenosine analogs, structure-activity relationships; Structure-Activity Relationship; structure-activity relationships; Structure-activity relationships-adenosine analogs; structure-activity relationships-relaxant effects on isolated ileal and aortic smooth muscle; Structure-activity relationships—adenosine analogs, smooth muscle relaxation and blood pressure depression
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600620911

The relaxant effects of a series of adenosine analogs were compared on isolated intestinal and aortic smooth muscle of the guinea pig. Blood pressure-lowering effects of these compounds were also compared in the guinea pig and dog. Analogs with a modified purine ring system (1-methyladenosine and toyocamycin) were more effective in relaxing intestinal than vascular smooth muscle. Substituents that decreased the basicity of the N1-position or interfered with hydrogen bonding in the 6-position decreased activity in both vascular and intestinal smooth muscle. Deoxyadenosine, which lacks an oxygen in the 2′-position of the ribose portion of the molecule, was ineffective in intestinal but still relaxed vascular smooth muscle. It was concluded that intestinal smooth muscle interacts significantly with the 2′-position of the ribose portion of the adenosine molecule whereas vascular smooth muscle requires an intact purine ring system in the molecule for maximal activity.