Cave Canem: Caniphedrine

Caniphedrine

The alkaloid L-ephedrine is found along with other alkaloids in plants of the genus Ephedra (e.g., Stapf, Ephedraceae). The herb has been used in Chinese medicine under the name Ma Huang for over 5000 years. In the 16th century pharmacopoeia Pentsao Kang Mu by Li Shih-Chen, it is recommended as a circulatory stimulant, diaphoretic, antipyretic, and cough suppressant (1). The ingredient responsible for its action, ephedrine, was isolated by Nagajosi Nagai in Tokyo in 1887 (2). Fig. 1. The pharmacological effects were elucidated by the Chinese Ku Kuei Chen and American Carl F. Schmidt in the 1920s and presented in a comprehensive monograph in 1930 (3). In their first experiment, the two researchers injected a dog with an ephedra extract. They observed a significant and sustained increase in blood pressure, an increase in heart rate, and vasoconstriction. In further experiments in animals, in self-experimentation and in volunteers, the pure substance ephedrine also caused bronchodilatation, relaxation of the bowels, pupil dilation, stimulation of the central nervous system and a decrease in urine volume (4). Since these effects largely corresponded to those of adrenaline, the two scientists concluded that it was a sympathomimetic; a direct and indirect one, as is now known. Unlike adrenaline, however, ephedrine was highly available when administered orally and its effects lasted longer. Based on these studies, ephedrine preparations were used in the following decades, for example, against hypotension, narcolepsy, asthma, bronchitis, allergy, rhinitis, obesity and enuresis nocturna. Fig. 2. structural comparison of L-ephedrine and L-adrenaline Today, ephedrine is obsolete in most of the above indications because it is nonspecific and newer substances with fewer adverse effects have been developed (5). For example, selective beta2-sympathomimetics are available for asthma and are administered with technically sophisticated inhalation devices. Ephedrine is still commercially available as a human drug in many countries as a solution for injection and in cold remedies (6). Away from the officially approved indications, there are reports of misuse of ephedrine as a party drug, as a medicated learning aid, for muscle building in bodybuilding, as a doping agent in sports, and as a precursor chemical for the synthesis of psychotropic substances (e.g., 7). Monopreparations with ephedrine are not available in many countries without a doctor’s prescription. However, in the drug forum of the website Eve & Rave (8), it is reported how one can allegedly obtain ephedrine tablets in a Swiss pharmacy: “(…) my friend came back from Switzerland today and had some with him. He just got them in a pharmacy, without a prescription. Said he needed them for his dog (incontinence). Was no problem he says.” Ephedrine, originally tested on dogs for human effects, is now actually used therapeutically in canids. Caniphedrine (Streuli) ad us. vet. contains the active ingredient L-ephedrine – HCl in dosages of 20 or 50 mg. The drug is used in veterinary medicine in bitches for urinary incontinence, which often occurs after castration (9, 10). Incontinence is the result of decreased urethral closure pressure after castration and can be treated efficiently with α-adrenergic agents (including phenylpropanolamine). Caniphedrine was originally allowed to be dispensed by pharmacists in many countries without a veterinary prescription (category C) – in large pack sizes of 100 or 500. Following the publication of several reports of possible abuse, caniphedrine was reclassified to category B and may only be dispensed with a veterinary prescription. Abuse of ephedrine is problematic. Severe cardiovascular and central nervous adverse effects can occur, especially in overdose, when other drugs are taken (interactions), and in the presence of underlying diseases (11, 12). Use as a party drug or for other abusive purposes must therefore be strongly discouraged.