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Compounds from this group, both used therapeutically or abused, comprise endogenous catecholamines (such as adrenaline and noradrenaline), synthetic amines (e.g., isoproterenol and dobutamine), trace amines (e.g., tyramine, tryptamine, histamine and octopamine), illicit drugs (e.g., ephedrine, cathinone, and cocaine), or even caffeine and synephrine. In addition to the effects triggered by stimulation of the sympathetic system, the discovery of trace amine associated receptors (TAARs) in humans brought new insights about their sympathomimetic pharmacology and toxicology. Although synthetic sympathomimetic agents are mostly seen as toxic, natural sympathomimetic agents are considered more complacently in the terms of safety in the vision of the lay public. Here, we aim to discuss the pharmacological and mainly toxicological aspects related to sympathomimetic natural agents, in particular of trace amines, compounds derived from plants like ephedra and khat, and finally cocaine. The main purpose of this review is to give a scientific and updated view of those agents and serve as a reminder on the safety issues of natural sympathomimetic agents most used in the community.<\/jats:p>","DOI":"10.3390\/biom12121793","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T07:10:27Z","timestamp":1669792227000},"page":"1793","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Natural Sympathomimetic Drugs: From Pharmacology to Toxicology"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0471-2756","authenticated-orcid":false,"given":"Vera Marisa","family":"Costa","sequence":"first","affiliation":[{"name":"UCIBIO, REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"Laborat\u00f3rio Associado i4HB\u2014Instituto para a Sa\u00fade e a Bioeconomia, Laborat\u00f3rio de Toxicologia, Departamento de Ci\u00eancias Biol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua Jorge Viterbo 228, 4050-313 Porto, Portugal"}]},{"given":"Luciana Grazziotin Rossato","family":"Grando","sequence":"additional","affiliation":[{"name":"Post-Graduation Program in Bioexperimentation, University of Passo Fundo (UPF), BR 285, Passo Fundo, S\u00e3o Jos\u00e9 99052-900, RS, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4738-3590","authenticated-orcid":false,"given":"Elisa","family":"Milandri","sequence":"additional","affiliation":[{"name":"UCIBIO, REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"Laborat\u00f3rio Associado i4HB\u2014Instituto para a Sa\u00fade e a Bioeconomia, Laborat\u00f3rio de Toxicologia, Departamento de Ci\u00eancias Biol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua Jorge Viterbo 228, 4050-313 Porto, Portugal"}]},{"given":"Jessica","family":"Nardi","sequence":"additional","affiliation":[{"name":"Post-Graduation Program in Bioexperimentation, University of Passo Fundo (UPF), BR 285, Passo Fundo, S\u00e3o Jos\u00e9 99052-900, RS, Brazil"}]},{"given":"Patr\u00edcia","family":"Teixeira","sequence":"additional","affiliation":[{"name":"UCIBIO, REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"Laborat\u00f3rio Associado i4HB\u2014Instituto para a Sa\u00fade e a Bioeconomia, Laborat\u00f3rio de Toxicologia, Departamento de Ci\u00eancias Biol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua Jorge Viterbo 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6076-6900","authenticated-orcid":false,"given":"P\u0159emysl","family":"Mlad\u011bnka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, 500 05 Hradec Kr\u00e1lov\u00e9, Czech Republic"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1382-5119","authenticated-orcid":false,"given":"Fernando","family":"Remi\u00e3o","sequence":"additional","affiliation":[{"name":"UCIBIO, REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"Laborat\u00f3rio Associado i4HB\u2014Instituto para a Sa\u00fade e a Bioeconomia, Laborat\u00f3rio de Toxicologia, Departamento de Ci\u00eancias Biol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua Jorge Viterbo 228, 4050-313 Porto, Portugal"}]},{"name":"on behalf of The OEMONOM","sequence":"additional","affiliation":[]}],"member":"1968","published-online":{"date-parts":[[2022,11,30]]},"reference":[{"key":"ref_1","unstructured":"Squire, L.R. 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