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The catecholamines comprise the endogenous substances dopamine, noradrenaline , and adrenaline , as well as numerous artificially synthesized compounds such as isoprenaline, an anti-bradycardiac medication. Their investigation comprises a major chapter in the history of physiology, biochemistry, and pharmacology. Adrenaline was the first hormone extracted from an endocrine gland and obtained in pure form, before the word hormone was coined. Adrenaline was also the first hormone whose structure and biosynthesis were discovered. Second to acetylcholine, adrenaline and noradrenaline were some of the first neurotransmitters discovered, and the first intercellular biochemical signals to be found in intracellular vesicles. The β-adrenoceptor was the first G protein-coupled receptor whose gene was cloned.