Natural Sympathomimetic Drugs: From Pharmacology to Toxicology

Abstract

Sympathomimetic agents are a group of chemical compounds that are able to activate the sympathetic nervous system either directly via adrenergic receptors or indirectly by increasing endogenous catecholamine levels or mimicking their intracellular signaling pathways. 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.

Establishing an Artificial Pathway for the Biosynthesis of Octopamine and Synephrine

“…Octopamine and synephrine exist widely in aquatic products and Citrus species, and their primary production approach is the extraction method. , Considering the limitations of animal and plant resources and harsh extraction conditions, biosynthetic octopamine and synephrine are essential substitutes for natural ones. Therefore, we proposed an enzyme synthetic pathway for producing octopamine and synephrine, which included a hydroxylation step from tyramine to generate octopamine and subsequently transform into synephrine (Figure ).…”

“…6,7 Synephrine, a crucial active alkaloid found in various plants, acts as a trace amine and an adrenergic agonist in humans. 1,8 Since the Food and Drug Administration (FDA) interdicted ephedrine-containing dietary products in 2004, synephrine's lipolysis made it the largescale popular supplement used in weight-loss products. 1,8 So far, the primary production methods of octopamine and synephrine have been extraction from aquatic products and Citrus species.…”

“…1,8 Since the Food and Drug Administration (FDA) interdicted ephedrine-containing dietary products in 2004, synephrine's lipolysis made it the largescale popular supplement used in weight-loss products. 1,8 So far, the primary production methods of octopamine and synephrine have been extraction from aquatic products and Citrus species. However, their production is limited by the low natural contents (octopamine 0.06−0.1% in fish sauce, synephrine 0.006−0.35% in Citrus sp.…”

“…However, their production is limited by the low natural contents (octopamine 0.06–0.1% in fish sauce, synephrine 0.006–0.35% in Citrus sp. ), long cycles, and separation efficiency. ,, The chemical synthesis of octopamine and synephrine was reported in the early days. However, the disadvantages, such as low yield, significant energy waste, and unfriendly environment caused by the structural complexity of natural materials, , have stymied its further development.…”

Hyperbaric oxygen therapy for the treatment of hypoxic/ischemic injury upon perinatal asphyxia—are we there yet?

“…It has also been used to treat or prevent hypotension. The mechanism of ephedrine action relies on increasing the stimulation of the postsynaptic α and β adrenergic receptors by norepinephrine ( 83 ). Ephedrine crosses the blood–brain barrier and stimulates the nervous system, and some amphetamine-and methamphetamine-like responses were attributed to ephedrine.…”