ABSTRACT
The history began in the 19th century with Ascanio Sobrero (1812-1888), the discoverer of glycerol trinitrate (nitroglycerine, NTG), and with Angelo Angeli (1864-1931), the discoverer of sodium trioxodinitrate (Angeli's salt). It is likely that Angeli and Sobrero never met, but their two histories will join each other more than a century later. In fact, it has been discovered that both NTG and Angeli's salt are able to induce a preconditioning effect. As NTG has a long history as an antianginal drug its newly discovered property as a preconditioning agent has also been tested in humans. Angeli's salt properties as a preconditioning and inotropic agent have only been tested in animals so far.
Subject(s)
Cardiovascular Agents/therapeutic use , Myocardial Reperfusion Injury/prevention & control , Nitric Oxide Donors/therapeutic use , Nitrites/therapeutic use , Nitroglycerin/therapeutic use , Vasodilator Agents/therapeutic use , Animals , Cardiovascular Agents/history , Cardiovascular Agents/metabolism , History, 19th Century , History, 20th Century , Humans , Myocardial Reperfusion Injury/history , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/physiopathology , Nitric Oxide/metabolism , Nitric Oxide Donors/history , Nitric Oxide Donors/metabolism , Nitrites/history , Nitrites/metabolism , Nitroglycerin/history , Nitroglycerin/metabolism , Signal Transduction/drug effects , Vasodilator Agents/history , Vasodilator Agents/metabolismABSTRACT
Shortly after the invention of nitroglycerin (NTG), it was noticed that this substance is capable of inducing a violent headache. Only recently, it became known that this was due to the release of nitric oxide (NO) by NTG. As the molecular mechanism of migraine pain remains to be determined, NTG, being pro-drug for NO, has been used to study the aetiology and pathophysiology of migraine. Such studies with NTG- and also histamine-induced headaches, have led to propose that NO may be the causative molecule in migraine pain. The evidence supporting the role of NO in migraine is discussed, e.g. substances capable of inducing experimental vascular headache do so with NO as the common mediator, while drugs with antimigraine activity inhibit NO and the cascade of intracellular reactions triggered by NO. The importance of NO as a potential initiator of the migraine attack opens new directions for the pharmacological treatment of migraine and other vascular headaches.
