In 2010 alone, it generated over US$9 billion in global sales. Theophylline was originally used as a bronchodilator, although its usage has declined due to several side effects such as seizures and cardiac arrhythmias caused by adenosine A1 receptor antagonism. Several herbs used in Traditional Chinese medicine contain drug compounds that are antagonists of P2X purinoreceptors. The following table provides an overview of these drug compounds and their interaction with purinergic receptors. Regadenoson, a vasodilator which acts on the adenosine A2A receptor, was approved by the United States Food and Drug Administration in 2008 and is currently widely used in the field of cardiology. Both adenosine and dipyridamole, which act on the A2A receptor, are used in myocardial perfusion imaging. Purinergic signalling is an important regulatory mechanism in a wide range of inflammatory diseases. It is understood that shifting the balance between purinergic P1 and P2 signalling is an emerging therapeutic concept that aims to dampen pathologic inflammation and promote healing. The following list of proposed medications is based on the workings of the purinergic signalling system:   The earliest reports of purinergic signalling date back to 1929, when the Hungarian physiologist Albert Szent-Györgyi observed that purified adenine compounds produced a temporary reduction in heart rate when injected into animals. In the 1960s, the classical view of autonomic smooth muscle control was based upon Dale's principle, which asserts that each nerve cell can synthesize, store, and release only one neurotransmitter. It was therefore assumed that a sympathetic neuron releases noradrenaline only, while an antagonistic parasympathetic neuron releases acetylcholine only. Although the concept of cotransmission gradually gained acceptance in the 1980s, the belief that a single neuron acts via a single type of neurotransmitter continued to dominate the field of neurotransmission throughout the 1970s. Beginning in 1972, Geoffrey Burnstock ignited decades of controversy after he proposed the existence of a non-adrenergic, non-cholinergic (NANC) neurotransmitter, which he identified as ATP after observing the cellular responses in a number of systems exposed to the presence of cholinergic and adrenergic blockers. Burnstock's proposal was met with criticism, since ATP is an ubiquitous intracellular molecular energy source so it seemed counter-intuitive that cells might also actively release this vital molecule as a neurotransmitter.