Ephedrine 346 Subject

Martin WR, Sloan JW, Sapira JD, et al Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther 12 245-258, 1971 McCormick TC Jr, McNeil TW Acute psychosis and Ritalin abuse. Tex State J Med... 

In a summary of the human abuse literature on anorectic phenylethylamines, Griffiths et al. (1979) found there was a good correlation between the results of self-administration studies in animals and information about the subjective effects and abuse in man. Specifically, amphetamine, diethyl-propion, and phenmetrazine have been associated with numerous clinical case reports involving abuse, and these three compounds as well as benz-phetamine and /-ephedrine have shown similar subjective effects in drug abuser populations (Griffiths et al. 1979). In addition, fenfluramine was associated with low incidence of abuse in humans and did not maintain self-injection responding in animals. Chlorphentermine was similarly associated with low incidence of abuse in man, but did not maintain selfinjection uniformly in animals (Griffiths et al. 1979). 

Even if some of the optically active spirophosphoranes mentioned above can exist as single species in the solid state, all of them are more or less rapidly transformed, when dissolved, into binary mixtures of diastereoisomers114-129 such as 12 and T3. However, a third type of synthesis yielded pure, optically active phosphoranes not subject to change when dissolved129. This was obtained by the stereospecific synthesis of the oxazaphos-pholidine 53130 (Scheme 5) derived from the —(1R, 2S)enantiomer of ephedrine by means... 

Ephedra is subject to the Dietary Supplement Health and Education Act (DSHEA), which was passed in 1994. The act essentially protects dietary supplements like ephedra. That is, while U.S. federal agencies can regulate prescription drug and food additives, DSHEA exempts herbal products and supplements from federal regulation. The law states that the United States Food and Drug Administration (FDA) cannot regulate dietary supplements unless, or until, they are proven to be unsafe and pose a risk to users. The United States Drug Enforcement Administration (DEA) monitors ephedrine because it can be used to make methamphetamine. 

A big concern about ephedra is that drug traffickers and laboratory operators are using ephedrine to make methamphetamines (speed). Consequently, in the United States, ephedrine is subject to regulatory laws. The Drug Enforcement Administration (DEA) carefully monitors medications containing ephedrine. 

Ephedra has a long history of legal use in the United States and around the world. Today, the laws that apply to ephedra cover sales, formulation, and labeling by manufacturers they do not outlaw its use by consumers as with street drugs such as marijuana and cocaine. Because ephedrine can be used to manufacture methamphetamine, companies that sell bulk ephedrine and ephedrine tablets are subject to laws... 

The enzymic oxidative deamination of simple phenethylamines is exemplified by the reported bio transformations of mescaline (146) (114, 115) and ephedrine (148) (116). Mescaline is metabolized to 3,4,5-trimethoxy-phenylacetic acid by tissue homogenates of mouse brain, liver, kidney, and heart (114,115). 3,4,5-Trimethoxybenzoic acid is also formed as a minor metabolite. The formation of jV-acetylmescaline (147), a significant metabolite in vivo, was not observed in the in vitro studies. Both D-(—)-and L-(+)-ephedrine have been incubated with enzyme preparations from rabbit liver norephedrine (149), benzoic acid, and 1-phenyl-1,2-propanediol were characterized as metabolites (116). The D-(—)-isomer was the better substrate, being more rapidly converted. Similar results were previously reported with rabbit liver slices as the source of enzyme (153,154). The enzymic degradation of the side chain of /i-phenethylamines has been extensively investigated with nonalkaloid substrates such as amphetamine (151) and jV-methylamphetamine (150) (10,155-157), and the reader is referred to these studies for a more comprehensive coverage of this aspect of the subject. 

For events in which output of energy is explosive (100 m sprint) stimulants, e.g. amphetamine, bro-mantan, carphendon, cocaine, ephedrine and caffeine (> 12 mg/1 in urine). Death has probably occured in bicycle racing (continuous hard exercise with short periods of sprint) due to h3q>erthermia and cardiac arrhythmia in metabolically stimulated and vaso-constricted subjects exercising maximally under a hot sun. 

The cardiovascular effects, subjective effects, and abuse potential of single intranasal doses of ephedrine 5 and 10 mg have been compared with oral doses of (—)ephe-drine 50 mg in 16 healthy Caucasian men with no drug/ alcohol/nicotine abuse or dependence (5). Intranasal ephedrine caused an increase in blood pressure but associated orthostatic hypotension. 

Berlin 1, Warot D, Aymard G, Acquaviva E, Legrand M, Labarthe B, Peyron 1, Diquet B, Lechat P. Pharmacodynamics and pharmacokinetics of single nasal (5 mg and 10 mg) and oral (50 mg) doses of ephedrine in healthy subjects. Eur J Clin Pharmacol 2001 57(6-7) 447-55. 

In a series of studies, Bell et al. assessed the effects of ephedrine mixtures on performance, and found measurable improvement. One and one-half hours after ingesting a placebo (P), caffeine (C) (4 mg/kg), ephedrine (E) (0.8 mg/kg), or caffeine and ephedrine, 12 subjects performed a 10-km run while wearing a helmet and backpack weighing 11 kg. The trials were performed in a climatic suite at 12-13°C, on a treadmill where the speed was regulated by the subject. V02, VC02, V(E), HR, and rating of perceived exer-... 

The rate at which any of the enantiomers is eliminated depends upon the urinary pH. At high pHs, excretion time is prolonged. At low pH ranges, excretion is accelerated. In controlled laboratory studies, where volunteer subjects were given either bicarbonate or ammonium chloride, the higher the urine pH, the more slowly the ephedrine and pseudoephedrine were excreted. Conversely, when the urine pH is low, excretion is accelerated (71). The importance of these observations is hard to assess, because without the addition of bicarbonate, urine pH values in the general population rarely approach 8.0. A study of pseudoephedrine pharmacokinetics in 33 volunteers who were not treated with drugs to alter urine pH found that these parameters could not be... 

Ephedrine and pseudoephedrine share properties with cocaine and with the amphetamines because they (1) stimulate (3-receptors directly, and (2) also cause the increased release of norepinephrine. Chronic exposure to abnormally high levels of circulating catecholamines can damage the heart. This is certainly the case with cocaine and methamphetamine (116,117), but ephedrine-related cardiomyopathy is an extremely rare occurrence, occurring only in individuals who take massive amounts of drug for prolonged periods of time. Only two papers have ever been published on the subject (118,119). 

Muittari A, Mattila MJ. Objective and subjective assessment of ephedrine combinations in asthmatic outpatients. Ann Clin Res 1979 11 (3) 87—89. 

Astrup A, Breum L, Toubro S, Hein P, Quaade F. The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet a double blind trial. Int J Obes Relat Metab Disord 1992 16(4) 269-277. 

Oxazolidines were easily and completely hydrolyzed at pH 1-11 at 37°C. The hydrolysis rates were subject to general acid-base catalysis by buffer substances and depended strongly on pH. Most oxazolidines showed sigmoidal pH-rate profiles with maximum rates at pH 7-7.5. At pH 7.4 and 37°C, the half-lives of hydrolysis for the various ephedrine oxazolidines (111) ranged from 5 seconds to 30 minutes (Scheme 18). The reaction rates in neutral and basic solutions decreased with... 

Ephedrine and pseudoephedrine have been measured in guinea pig plasma using HPLC with fluorescence detection, following precolumn derivatization with 5-dimethylamino-napthalene-1-sulfonyl chloride in acetonitrile. The mobile phase was 0.6% phosphate buffer (pH 6.5)-methanol (3 8 v/v). Jacob et al. developed an LC-atmospheric pressure chemical ionization MS-MS method for the quantitaion of various alkaloids found in ephedra-containing dietary supplements and also in plasma and urine from subjects using these supplements. Using this method, the concentrations of ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, methylephedrine, methylpseudoephedrine and caffeine were determined in low nanogram quantities in plasma and urine. The analytical cycle time for this method was 12 min. 

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