Ephedrine

Other Names Aphetonin, efedrina, ephedrin, ephedrine, ephedrinum, ephetonin, erythro-2-methylaminoI- hydroxyl-l-phenylpropane, (IR,2S)-2-methylamino- l-phenyl-l-propanol Empirical formula: ClQH1SNO Substance type: ephedra alkaloid Ephedrine was first isolated in 1887 by Nagai from Ephedra distachya (cf. Ephedra spp.) and was first introduced into ophthalmology as Mydriaticum (cf. atropine). Since around 1925, the alkaloid also been an important asthma medication (Schneider 1974,2:54*). Ephedrine occurs in almost all species of ephedra (cf. Ephedra gerardiana, Ephedra sinensis, Ephedra spp.). Two Malvaceae, Sida acuta Burm. and Sida rhombifolia 1. (Sida spp.), which are smoked along the Mexican Gulf Coast as a lTlarijuana substitute (cf. Cannabis indica), also contain ephedrine (Schultes and Hoffmann 1992, 56*). Ephedrine is probably present in other species of Sida as well. Ephedrine has also been found in Aconitum spp., yew (Taxus bacata L.; cf. witches' ointments), and khat (Catha edulis) (Rompp 1995, 1191*; Roth et al. 1994,695*). Ephedrine has sympathomimetic effects and causes an increased excretion of the endogenous neurotransmitter noradrenaline, which is responsible for the stimulant effects (Kalix 1991). Ephedrine hydrochloride has potent stimulant effects; it improves the general mood and may even induce euphoria. These effects can last up to eight hours. It is known that "therapeutic overdoses of ephedrine (Aphetonin) can also cause pronounced states of excitation combined with sexual arousal" (Fiihner 1943, 199*). In men, however, ephedrine induces a temporary state of impotence. Ephedrine is a popular doping agent for athletes but is prohibited for this purpose (Korner 1994, 1483*). There have been reports of "ephedrine addiction" (Prokop 1968). Because ephedrine helps reduce swelling of the mucous membranes, it is a component of rnany cough syrups (see codeine). Ephedrine suppresses the effects of alcohol and is administered subcutaneously to prevent hypotension during anesthesia (Morton 1977,35*). Between 55 and 75% of ephedrine is excreted in the urine unchanged (Roth et al. 1994, 812*). The effective oral dosage is 5 to 10 mg. The closely related ephedra alkaloids have similar effects but vary in their potency (Reti 1953). Pseudoephedrine is significantly weaker, while the related ephedroxanes tend to have depressant effects (Hikino et al. 1985). Pseudoephedrine can be used to produce methcathinone, which in the United States is smoked as "speed" or snuffed like cocaine (it is also used as a substitute for cocaine) (Glennon et al. 1987). Although Catha edulis does contain d- norisoephedrine, it is not the plant's primary active constituent, as was previously assumed (Wolfes 1930). However, cathinone, the psychoactive constituent in khat leaves, is metabolized into ephedrinene (Brenneisen et al. 1986; Kalix 1991). Norephedrine, the nor-form (a threo-isomer) of ephedrine, lacks a methyl group on the side chain. Up to 90% of norephedrine is excreted unchanged (Cho and Segal 1994, 58). Removing the hydroxyl group from the ephedrine molecule by either reduction or ~hydroxylation yields amphetamine (Cho and Segal 1994,57). Amphetamine is one of the most highly effective stimulants known. Numerous derivatives have been developed from amphetamine (e.g., Ritalin, methamphetamine, MDMA; cf. herbal ecstasy). In addition to their stimulating effects, several of these substances also induce empathogenic and even hallucinogenic effects (Cho and Segal 1994). Amphetamine has not yet been found to occur in nature.

Commercial Forms and Regulations Ephedrine is available as anhydrous ephedrine (ephedrinum anhydricum), ephedrine hemihydrate, or (most often) ephedrine hydrochloride ([ +] -ephedrine-HCL). Ephedrine and ephedrine preparations (medicinal drugs) require a prescription. Because ephedrine is now regarded as a precursor substance for the illegal synthesis of MDMA, it is only rarely prescribed and is strictly controlled. In Germany, only combination preparations (cough medicines) in which a single dosage may not exceed 10 mg of ephedrine can be purchased in a pharmacy without prescription (Roth et al. 1994, 812*). A number of high-profile cases, including one in which a young professional athlete died after ingesting ephedrine before training, resulted in the banning of most ephedrine preparations in the United States in 2004. Literature See also the entries for Catha edulis, Ephedra gerardiana, Ephedra sinica, and Ephedra spp. Brenneisen, R., S. Geisshusler, and X. Schorno. 1986. Metabolism of cathinone to (-)-norephedrine and (-)-norpseudoephedrine. Journal of Pharmacy and Pharmacology 38:298-300. Cho, Arthur K., and David S. Segal, eds. 1994. Amphetamine and its analogs: Psychopharmacology, toxicology and abuse. San Diego: Academic Press. Costa, E., and S. Garattini, eds. 1970. Amphetamine and related compounds. New York: Raven Press. Glennon, R., M. Yousif, N. Naiman, and P. Kalix. 1987. Methcathinone, a new and potent amphetamine-like agent. Pharmacol. Biochem. Behav.26:547-51. Hikino, Hiroshi, Kuniaki Ogata, Yoshimasa Kasahara, and Chohachi Konno. 1984. Pharmacology of ephedroxanes. Journal of Ethnopharmacology 13:175-9l. Hofmann, H., K. Opitz, and H. J. Schnelle. 1955. Die Wirkung des nor-c-Ephedrins. ArzneimittelForshung 5:367-70. Kalix, P. 1991. The pharmacology of psychoactive alkaloids from Ephedra and Catha. Journal of Ethnopharmacology 32:201-8. Panse, E, and W. Klages. 1964. Klinischpathologische Beobachtungen bei chronischem MiBbrauch von Ephedrin. Archiv fur Psychiatrie und Neurologie 206:69 ff. Prokop, H. 1968. Halluzinose bei Ephedrinsucht. Der Nervenarzt 1968:71 ff. Reti, L. 1953. Ephedra bases. In The alkaloids: Chemistry and physiology, ed. R. H. E Manske and H. L. Holmes, 339-62. New York: Academic Press. Wolfes, 0.1930. Uber das Vorkommen von dNorisoephedrin in Catha edulis. Archiv der Pharmazie 268:81-83.