The intent of this study is to see if the rate that the body breaks down l-methamphetamine (l-MA) could be used as an accurate estimate for the rate that the body breaks down d-methamphetamine (d-MA). l-MA is sold over the counter as a nasal decongestant where as d-MA is the commonly abused form of methamphetamine.

Start Date01 Oct 2008

Sponsor / Collaborator

California Pacific Medical Center Research Institute

[+3]

100 Clinical Results associated with Levmetamfetamine

100 Translational Medicine associated with Levmetamfetamine

100 Patents (Medical) associated with Levmetamfetamine

Literatures (Medical) associated with Levmetamfetamine

01 May 2024·Pharmacology Biochemistry and Behavior

Enantiomeric contributions to methamphetamine's bidirectional effects on basal and fentanyl-depressed respiration in mice

Article

Author: Walentiny, D Matthew ; Elder, Harrison J ; Beardsley, Patrick M

RATIONALEFentanyl remains the primary cause of fatal overdoses, and its co-use with methamphetamine (METH) is a growing concern. We previously demonstrated that racemic METH can either enhance or mitigate opioid-induced respiratory depression (OIRD) dependent upon whether a low or high dose is administered. The optical isomers of METH, dextromethamphetamine (d-METH) and levomethamphetamine (l-METH), differ substantially in their selectivity and potency to activate various monoamine (MA) receptors, and these pharmacological differences may underlie the bidirectional effects of the racemate. Since it is unknown which of METH's MA receptor mechanisms mediate these respiratory effects, examination of METH's pharmacologically distinct enantiomers may provide insight into treatment targets for OIRD.METHODSThe two optical isomers of METH, d-METH and l-METH, were tested in adult male mice to determine their effects on basal and fentanyl-depressed respiratory frequency, tidal volume, and minute ventilation (MVb; i.e., respiratory frequency x tidal volume) using whole-body plethysmography.RESULTSWhen tested at dose ranges of 1.0-10 mg/kg, d-METH elevated MVb and l-METH decreased basal MVb. A dose of 30 mg/kg l-METH increased basal MVb. Under fentanyl-depressed conditions, the bidirectional effects of racemic METH were observed with d-METH treatment while l-METH significantly exacerbated OIRD at 1.0 and 3.0 mg/kg.CONCLUSIONSd-METH and l-METH differentially contribute to the bidirectional respiratory modulation observed by the racemate, with d-METH exhibiting predominantly stimulatory effects and l-METH exhibiting primarily depressant effects depending on dose.

01 Nov 2001·Drug metabolism and disposition: the biological fate of chemicals

CYP2B6 and CYP2C19 as the major enzymes responsible for the metabolism of selegiline, a drug used in the treatment of Parkinson's disease, as revealed from experiments with recombinant enzymes.

Article

Author: Oscarson, M ; Turpeinen, M ; Salonen, J S ; Pelkonen, O ; Ingelman-Sundberg, M ; Nyman, L ; Hidestrand, M

In view of conflicting data in the literature regarding the enzyme(s) responsible for metabolism of selegiline, a drug used in the treatment of Parkinson's disease, investigations were carried out in vitro using the human cytochrome P450 enzymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 recombinantly expressed in yeast to elucidate the enzyme specificity in selegiline metabolism. In the yeast microsomes used, desmethylselegiline and levomethamphetamine were formed from selegiline at significant rates. The highest contribution to the hepatic clearance of selegiline was calculated to be exerted by CYP2B6 (124 l/h) CYP2C19 (82 l/h), whereas CYP3A4 (27 l/h) and CYP1A2 (21 l/h) were of less importance. Antibodies against CYP2B6 inhibited metabolism of selegiline in microsomes containing CYP2B6 but not in microsomes without significant amounts of the enzyme. In contrast to previous reports, we could not find any role for CYP2D6 in the metabolism of selegiline. The data strongly indicate that the high extent of interindividual variation seen in vivo for selegiline clearance is caused by the metabolism of the compound by the highly polymorphic CYP2B6 and CYP2C19.

01 Aug 1997·Clinical PharmacokineticsQ2 · MEDICINE

Clinical Pharmacokinetics and Pharmacodynamics of Selegiline

Q2 · MEDICINE

Review

Author: Mahmood, I

Selegiline is a selective inhibitor of monoamine oxidase-B (MAO-B) at a dose of 10 mg/day and is given to patients with Parkinson's disease as an adjunct to levodopa therapy. By inhibiting MAO-B, selegiline increases the dopamine levels in the substantia nigra. Selegiline also blocks dopamine re-uptake from the synaptic cleft, thus increasing the dopamine concentrations in the brain. At a dose of 10 mg/day, selegiline is devoid of 'cheese effect'. The pharmacokinetics of selegiline are highly variable. Following an oral dose of selegiline 10 mg, it is rapidly absorbed and metabolised to desmethylselegiline, levoamphetamine and levomethamphetamine. The mean peak plasma concentration (Cmax) is approximately 2 micrograms/L and the time to reach the peak is under an hour. The absolute bioavailability of selegiline is approximately 10%. It has an apparent volume of distribution of 1854 L. The oral clearance of selegiline (59 L/min) is many fold higher than the liver blood flow (1.5 L/min), indicating that extrahepatic processes are involved in the elimination of selegiline. The elimination half-life of selegiline is about 1.5 hours. Following multiple administration of selegiline 10 mg/day, the accumulation of both the parent compound and its metabolites have been reported. At least a 4-fold increase in the half-lives of selegiline and desmethylselegiline has been reported. There is at least a 3-fold increase in the Cmax and area under the concentration-time curve of selegiline with food. One of the metabolites of selegiline, desmethylselegiline, is believed to posses some MAO-B inhibitory property, though to a lesser extent than that of selegiline. Within 2 to 4 hours of an oral dose of selegiline 10 mg, 86% of the platelet MAO-B activity was inhibited and it took almost 2 weeks for platelet MAO-B activity to return to the baseline values. Transdermal administration of selegiline resulted in an increase in the plasma concentrations of selegiline and a decrease in the formation of its metabolites, indicating that the extensive first-pass effect is avoided when selegiline is given transdermally.

100 Deals associated with Levmetamfetamine

External Link

KEGG	Wiki	ATC	Drug Bank
D02291	Levmetamfetamine	R01A	DB09571

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Indication	Country/Location	Organization	Date
Nasal Obstruction	-	-	-

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Indication	Highest Phase	Country/Location	Organization	Date
Cognition Disorders	Preclinical	GB	Cognition Pharmaceuticals, LLC	-

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