Levomethamphetamine (INN: levmetamfetamine) is an optical isomer of methamphetamine primarily used as a topical nasal decongestant. Levomethamphetamine is used to treat nasal congestion from allergies and the common cold. It was first used medically as decongestant beginning in 1958 and has been used for such purposes, primarily in the United States, since then. Levomethamphetamine is significantly less potent in terms of physiologic and subjective drug effects than racemic methamphetamine, dextromethamphetamine, and related amphetamines, especially when used as a nasal decongestant at therapeutic doses.
Medical uses Levomethamphetamine is used to treat nasal congestion related to the common cold and allergic rhinitis. It is available in the form of an inhaler containing 50 mg total per inhaler and delivering between 0.04 and 0.15 mg of the drug per inhalation. Inhalers with a total of 113 mg levomethamphetamine were previously marketed in the United States, but the total amount was eventually reduced to 50 mg.
Side effects When the nasal decongestant is taken in excess, levomethamphetamine has potential side effects. These would be similar to those of other decongestants.
Pharmacology
Pharmacodynamics
Levomethamphetamine acts as a selective norepinephrine releasing agent. The potencies of levomethamphetamine, levoamphetamine, dextromethamphetamine, and dextroamphetamine in terms of norepinephrine release in vitro and in vivo in rats are all similar. Conversely, whereas dextromethamphetamine and dextroamphetamine are relatively balanced releasers of dopamine and norepinephrine in vitro, levomethamphetamine is about 15- to 20-fold less potent in inducing dopamine release relative to norepinephrine release. Moreover, whereas levoamphetamine is about 3- to 5-fold less potent in terms of dopamine release than dextroamphetamine in vivo, levomethamphetamine is dramatically less potent than dextromethamphetamine and substantially less potent than levoamphetamine in this regard. In accordance with the findings of catecholamine release studies, levomethamphetamine is 2- to 10-fold or more less potent than dextromethamphetamine in terms of psychostimulant-like effects in rodents. For comparison, levoamphetamine is only 1- to 4-fold less potent than dextroamphetamine in its stimulating and reinforcing effects in monkeys and humans. The effects of levomethamphetamine are qualitatively distinct relative to those of racemic methamphetamine and dextromethamphetamine and it does not possess the same potential for euphoria or addiction that these drugs possess. In clinical studies, levomethamphetamine at oral doses of 1 to 10 mg has been found not to affect subjective drug responses, heart rate, blood pressure, core temperature, electrocardiography, respiration rate, oxygen saturation, or other clinical parameters. As such, doses of levomethamphetamine of less than or equal to 10 mg have no significant physiological or subjective effects. However, higher doses of levomethamphetamine, for instance 0.25 to 0.5 mg/kg (mean doses of ~18–37 mg) intravenously, have been reported to produce significant pharmacological effects, including increased heart rate and blood pressure, increased respiration rate, and subjective effects like intoxication and drug liking. On the other hand, in contrast to dextromethamphetamine, levomethamphetamine also produces subjective "bad" or aversive drug effects. Among the physiological effects of levomethamphetamine is vasoconstriction, which makes it useful for nasal decongestion. For comparison to levomethamphetamine, 5 to 60 mg oral doses of the related drug levoamphetamine have been used clinically and have been reported to produce significant pharmacological effects, for instance on wakefulness and mood. In addition to its norepinephrine-releasing activity, levomethamphetamine is also an agonist of the trace amine-associated receptor 1 (TAAR1). Levomethamphetamine has also been found to act as a catecholaminergic activity enhancer (CAE), notably at much lower concentrations than its catecholamine releasing activity. It is 1- to 10-fold less potent than selegiline but is 3- to 5-fold more potent than dextromethamphetamine in this action. The CAE effects of such agents may be mediated by TAAR1 agonism.
Pharmacokinetics
Absorption The bioavailability of levomethamphetamine is approximately 100%. The peak levels of levomethamphetamine range from 3.3 to 31.4 ng/mL with single oral doses of 1 to 10 mg and from 65.4 to 125.9 ng/mL with single intravenous doses of 0.25 to 0.5 mg/kg. The area-under-the-curve (AUC) levels of levomethamphetamine range from 73.0 to 694.7 ng⋅h/mL with single oral doses of 1 to 10 mg and from 1,190.7 to 2,368.1 mg/kg with single intravenous doses of 0.25 to 0.5 mg/kg.
Distribution The volume of distribution of levomethamphetamine is 288.5 to 315.5 L or 4.15 to 4.17 L/kg.
Metabolism The pharmacokinetics of levomethamphetamine generated as a metabolite from selegiline have been found to be significantly different in CYP2D6 poor metabolizers versus extensive metabolizers. Area-under-the-curve (AUC) levels of levomethamphetamine were 46% higher and its elimination half-life was 33% longer in CYP2D6 poor metabolizers compared to extensive metabolizers. These findings suggest that CYP2D6 may be significantly involved in the metabolism of levomethamphetamine. Levomethamphetamine is metabolized into levoamphetamine in small amounts.
Elimination Levomethamphetamine is excreted in urine 40.8 to 49.0% as unchanged levomethamphetamine and 2.1 to 3.3% as levoamphetamine. Levomethamphetamine can register on urine drug tests as either methamphetamine, amphetamine, or both, depending on the subject's metabolism and dosage. Levomethamphetamine metabolizes completely into levoamphetamine after a period of time. The mean elimination half-life of levomethamphetamine ranges between 10.2 and 15.0 hours. For comparison, the elimination half-life of dextromethamphetamine was around 10.2 to 10.7 hours in the same studies. The clearance of levomethamphetamine is 15.5 to 19.1 L/h or 0.221 L/h⋅kg. With selegiline at an oral dose of 10 mg, levomethamphetamine and levoamphetamine are eliminated in urine and recovery of levomethamphetamine is 20 to 60% (or about 2–6 mg) while that of levoamphetamine is 9 to 30% (or about 1–3 mg).
… excerpt ends here. Continue reading the full article.
