Document Detail


Cerebral blood flow effects of the nitric oxide donor, nitroglycerin and its drug combinations in the non-human primate model.
MedLine Citation:
PMID:  10514899     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nitroglycerin (CAS 55-63-0, Nitrocene) has successfully been used in the management of angina during the last several decades. Although important information on the pharmacological actions and efficacy of nitroglycerin have been extracted, to date, limited research has been conducted on its effects on cerebral blood flow. In recent years, with the aid of SPECT (single photon emission computed tomography) and PET (positron emission tomography) it has been shown that marked cerebral blood flow changes occur under treatment of a wide variet of drugs. Illucidation of the pharmacological mode of action of nitroglycerin has gained momentum with the discovery of nitric oxide (NO) as an endogenous mediator and with the knowledge that nitroglycerin acts as a NO donor. The present study investigated the effects of nitroglycerin (0.25 microgram/kg/min over 10 min) on the cerebral blood flow, using 99mTc-HMPAO (hexamethylpropylene amine oxime) and SPECT, in an anaesthetised primate model, as well as the effects of its drug interactions with therapeutic agents that influence cerebrovascular dynamics, e.g. sumatriptan, nimodipine and acetazolamide. The present study with nitroglycerin indicates that the response time to measure cerebral blood flow effects seems to be present and an important factor as the transient is relatively short. The current treatment regime with nitroglycerin indicates a slight increase, when compared with control control results, although not significant, except for regional significant increases in particular the occipital regions of the brain. Drug interaction between nitroglycerin and nimodipine may occur as a reduction of 20% in cerebral blood flow from the control control was observed in this case. The results for the combination of nitroglycerin with sumatriptan showed a further increase of the cerebral blood flow to near significance, when compared with the control results and is significantly increased (+27%) when compared with sumatriptan treatment alone. Effective treatment with sumatriptan may therefore be compromised with simultaneous administration of nitroglycerin or NO donor drugs. The combination of nitroglycerin and acetazolamide suggested that the increase in cerebral blood flow is primarily attributed to the influence of acetazolamide. The cerebral blood flow effects of these drugs and possible interactions during an angina attack need to be investigated.
Authors:
D W Oliver; I C Dormehl
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arzneimittel-Forschung     Volume:  49     ISSN:  0004-4172     ISO Abbreviation:  Arzneimittelforschung     Publication Date:  1999 Sep 
Date Detail:
Created Date:  1999-11-23     Completed Date:  1999-11-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372660     Medline TA:  Arzneimittelforschung     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  732-9     Citation Subset:  IM    
Affiliation:
Faculty Pharmacy, Pharmacology, Potchefstroom University for Christian Higher Education, South Africa. fkldwo@puknet.puk.ac.za
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MeSH Terms
Descriptor/Qualifier:
Acetazolamide / administration & dosage,  pharmacology
Algorithms
Animals
Blood Pressure / drug effects
Brain / blood supply,  radionuclide imaging
Calcium Channel Blockers / administration & dosage,  pharmacology
Carbonic Anhydrase Inhibitors / administration & dosage,  pharmacology
Cerebrovascular Circulation / drug effects*
Dose-Response Relationship, Drug
Drug Combinations
Heart Rate / drug effects
Male
Nimodipine / administration & dosage,  pharmacology
Nitric Oxide Donors / administration & dosage,  pharmacology*
Nitroglycerin / administration & dosage,  pharmacology*
Papio
Sumatriptan / administration & dosage,  pharmacology
Vasoconstrictor Agents / administration & dosage,  pharmacology
Vasodilator Agents / administration & dosage,  pharmacology*
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Carbonic Anhydrase Inhibitors; 0/Drug Combinations; 0/Nitric Oxide Donors; 0/Vasoconstrictor Agents; 0/Vasodilator Agents; 103628-46-2/Sumatriptan; 55-63-0/Nitroglycerin; 59-66-5/Acetazolamide; 66085-59-4/Nimodipine

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


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