Abstract |
Several members of the heterocyclic family 3-selena-7-azabicyclo[3.3.1] nonane have been synthesized and characterized via IR, 1H, 13C, 15N, and 77Se NMR spectroscopy and, in some cases, by X-ray diffraction analysis. Select members, namely the hydroperchlorates of the amines, were examined for antiarrhythmic properties in anesthetized dogs in which myocardial infarctions were induced by techniques previously described. In the predrug, or control state, sustained ventricular tachycardia were induced by ventricular paced beats at rates above 300/min. When 7-benzyl-3-selena-7-azabicyclo[3.3.1] nonane hydroperchlorate was administered at 3 and 6 mg/kg, the sustained ventricular tachycardia could no longer be induced. Similar doses of lidocaine, a commonly used antiarrhythmic, caused slowing of the sustained ventricular tachycardia below 300/min but did not abolish their inducibility. In addition, select members of the hydroperchlorates caused a moderate 10-20% increase in mean blood pressure whereas lidocaine caused either no change in or slightly reduced mean blood pressure. Some general conclusions are delineated concerning the structural requirements that appear to be necessary for activity in this family of heterocycles and that have not been reported previously.
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Authors | M D Thompson, G S Smith, K D Berlin, E M Holt, B J Scherlag, D van der Helm, S W Muchmore, K A Fidelis |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 30
Issue 5
Pg. 780-8
(May 1987)
ISSN: 0022-2623 [Print] United States |
PMID | 3572967
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Bridged Bicyclo Compounds
- Bridged-Ring Compounds
- Lidocaine
- Selenium
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Topics |
- Animals
- Arrhythmias, Cardiac
(drug therapy)
- Bridged Bicyclo Compounds
(chemical synthesis, therapeutic use)
- Bridged-Ring Compounds
(therapeutic use)
- Chemical Phenomena
- Chemistry
- Chemistry, Physical
- Dogs
- Lidocaine
(therapeutic use)
- Magnetic Resonance Spectroscopy
- Molecular Conformation
- Selenium
(therapeutic use)
- Tachycardia
(drug therapy)
- X-Ray Diffraction
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