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Levofenfluramine (INN), or (−)-3-trifluoromethyl-N-ethylamphetamine, also known as (−)-fenfluramine or (R)-fenfluramine, is a drug of the amphetamine family that, itself (i.e., in enantiopure form), was never marketed.<ref name="Hall1996">{{#invoke:citation/CS1|citation |CitationClass=book }}</ref> It is the levorotatory enantiomer of fenfluramine, the racemic form of the compound, whereas the dextrorotatory enantiomer is dexfenfluramine.<ref name="Pool2001">{{#invoke:citation/CS1|citation |CitationClass=book }}</ref> Both fenfluramine and dexfenfluramine are anorectic agents that have been used clinically in the treatment of obesity (and hence, levofenfluramine has been as well since it is a component of fenfluramine).<ref name="Pool2001" /> However, they have since been discontinued due to reports of causing cardiovascular conditions such as valvular heart disease and pulmonary hypertension,<ref name="pmid12357124">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> adverse effects that are likely to be caused by excessive stimulation of 5-HT2B receptors expressed on heart valves.<ref name="pmid20716786">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref><ref name="pmid11104741">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

Dexfenfluramine is believed to be solely responsible for the appetite suppressant properties of fenfluramine,<ref name="Pool2001" /> of which it has been demonstrated to mediate predominantly via activation of postsynaptic 5-HT1B and 5-HT2C receptors<ref name="pmid20647205">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> through a combination of indirect serotonin releasing agent and direct serotonin receptor agonist activities (the latter of which are mediated fully by its active metabolite dexnorfenfluramine).<ref name="pmid11888573">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref><ref name="pmid16249524">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref><ref name="pmid14752059">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> Contrarily, levofenfluramine is thought to contribute only to unwanted side effects.<ref name="Pool2001" /> Paradoxically, however, it has been shown that levofenfluramine too acts as a relatively potent releaser of serotonin,<ref name="pmid17017961">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> though with approximately 1/3rd of the efficacy of dexfenfluramine,<ref name="pmid17017961" /> As such, it would be expected to possess some degree of appetite suppressant properties as well, yet it does not.<ref name="Pool2001" /><ref name="O'Donnell-Ahuja2005">{{#invoke:citation/CS1|citation |CitationClass=book }}</ref> A potential explanation as to why levofenfluramine is not similarly an effective anorectic is that it has also been found to behave as a dopamine receptor antagonist,<ref name="pmid9824670">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> which, as dopamine antagonists like atypical antipsychotics are associated with causing increased appetite and weight gain—effects that their actions on dopamine receptors have been implicated in playing a role in the development of,<ref name="pmid19931306">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> is an action that could in theory cancel out the hypothetical serotonergically-mediated appetite suppressant effects of the compound. Of course, this is merely speculation and has not been proven.

Levonorfenfluramine, an active metabolite of levofenfluramine, is also a fairly potent serotonin releasing agent (with a potency of approximately 1/2 that of norfenfluramine and 1/6th that of dexfenfluramine) and, similarly to dexnorfenfluramine, 5-HT2B and 5-HT2C receptor agonist, as well as a somewhat less potent norepinephrine reuptake inhibitor (about 1/2 that of its efficacy as a serotonin releaser).<ref name="pmid11104741" /><ref name="pmid11888573" /><ref name="pmid17017961" /> As such, likely contributes significantly to the biological activity—though not necessarily appetite suppressant effects—of not only levofenfluramine but of racemic fenfluramine as well. In contrast to levonorfenfluramine, levofenfluramine is virtually inactive as a reuptake inhibitor or releaser of norepinephrine,<ref name="pmid17017961" /> and neither compound has any effect on dopamine reuptake or release.<ref name="pmid17017961" />


Levofenfluramine sections
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Levofenfluramine (INN), or (−)-3-trifluoromethyl-N-ethylamphetamine, also known as (−)-fenfluramine or (R)-fenfluramine, is a drug of the amphetamine family that, itself (i.e., in enantiopure form), was never marketed.<ref name="Hall1996">{{#invoke:citation/CS1|citation |CitationClass=book }}</ref> It is the levorotatory enantiomer of fenfluramine, the racemic form of the compound, whereas the dextrorotatory enantiomer is dexfenfluramine.<ref name="Pool2001">{{#invoke:citation/CS1|citation |CitationClass=book }}</ref> Both fenfluramine and dexfenfluramine are anorectic agents that have been used clinically in the treatment of obesity (and hence, levofenfluramine has been as well since it is a component of fenfluramine).<ref name="Pool2001" /> However, they have since been discontinued due to reports of causing cardiovascular conditions such as valvular heart disease and pulmonary hypertension,<ref name="pmid12357124">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> adverse effects that are likely to be caused by excessive stimulation of 5-HT2B receptors expressed on heart valves.<ref name="pmid20716786">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref><ref name="pmid11104741">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

Dexfenfluramine is believed to be solely responsible for the appetite suppressant properties of fenfluramine,<ref name="Pool2001" /> of which it has been demonstrated to mediate predominantly via activation of postsynaptic 5-HT1B and 5-HT2C receptors<ref name="pmid20647205">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> through a combination of indirect serotonin releasing agent and direct serotonin receptor agonist activities (the latter of which are mediated fully by its active metabolite dexnorfenfluramine).<ref name="pmid11888573">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref><ref name="pmid16249524">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref><ref name="pmid14752059">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> Contrarily, levofenfluramine is thought to contribute only to unwanted side effects.<ref name="Pool2001" /> Paradoxically, however, it has been shown that levofenfluramine too acts as a relatively potent releaser of serotonin,<ref name="pmid17017961">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> though with approximately 1/3rd of the efficacy of dexfenfluramine,<ref name="pmid17017961" /> As such, it would be expected to possess some degree of appetite suppressant properties as well, yet it does not.<ref name="Pool2001" /><ref name="O'Donnell-Ahuja2005">{{#invoke:citation/CS1|citation |CitationClass=book }}</ref> A potential explanation as to why levofenfluramine is not similarly an effective anorectic is that it has also been found to behave as a dopamine receptor antagonist,<ref name="pmid9824670">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> which, as dopamine antagonists like atypical antipsychotics are associated with causing increased appetite and weight gain—effects that their actions on dopamine receptors have been implicated in playing a role in the development of,<ref name="pmid19931306">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> is an action that could in theory cancel out the hypothetical serotonergically-mediated appetite suppressant effects of the compound. Of course, this is merely speculation and has not been proven.

Levonorfenfluramine, an active metabolite of levofenfluramine, is also a fairly potent serotonin releasing agent (with a potency of approximately 1/2 that of norfenfluramine and 1/6th that of dexfenfluramine) and, similarly to dexnorfenfluramine, 5-HT2B and 5-HT2C receptor agonist, as well as a somewhat less potent norepinephrine reuptake inhibitor (about 1/2 that of its efficacy as a serotonin releaser).<ref name="pmid11104741" /><ref name="pmid11888573" /><ref name="pmid17017961" /> As such, likely contributes significantly to the biological activity—though not necessarily appetite suppressant effects—of not only levofenfluramine but of racemic fenfluramine as well. In contrast to levonorfenfluramine, levofenfluramine is virtually inactive as a reuptake inhibitor or releaser of norepinephrine,<ref name="pmid17017961" /> and neither compound has any effect on dopamine reuptake or release.<ref name="pmid17017961" />


Levofenfluramine sections
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