Character Analysis: Levetiracetam
Levetiracetam
Levetiracetam is probably a major breakthrough in the treatment of epilepsies. It is a highly effective, broad-spectrum, one of second generation AED with a unique mechanism of action.
Chemical structure:
Levetiracetam is a single enantiomer, (S)-α-ethyl-2-oxo-pyrrolidine acetamide. Its molecular formula is C8H14N2O2 and its molecular weight is 170.21. It is chemically unrelated to any of the other antiepileptic drugs. It is a white to off-white powder with a faint odor and bitter taste and highly soluble in water (104.0 g/100 mL). It is freely soluble in chloroform (65.3 g/100 mL) and in methanol (53.6 g/100 mL), soluble in ethanol (16.5 g/100 mL), sparingly soluble in acetonitrile (5.7 g/100 mL) and practically insoluble in …show more content…
Its antiepileptic activity does not involve a direct interaction with any of the other AEDs. In contrast, levetiracetam has been observed to exert several atypical electrophysiological actions, including a moderate inhibition of high voltage-gated N-type Ca2+ channels, reduction of intracellular Ca2+ release from the endoplasmic reticulum, as well as suppression of GABA responses at the GABA-A receptor and glycine-gated currents by blocking its negative allosteric modulation by beta-carbolines and …show more content…
These mice seem normal at birth, but develop unusually severe seizures by 1 or 2 weeks of age and die within 3 weeks after birth.199 Brain membranes and purified synaptic vesicles from mice lacking SV2A did not bind a tritiated derivative of levetiracetam, indicating that SV2A is necessary for levetiracetam binding. Levetiracetam and related derivatives bind to SV2A, but not to the related isoforms SV2B and SV2C expressed in fibroblasts, indicating that SV2A is sufficient for levetiracetam binding. In contrast, none of the other AEDs tested revealed any binding to SV2A. The severe seizures observed in mice lacking SV2A support the interpretation that this protein influences mechanisms of seizure generation or propagation.
Pharmacokinetics
Levetiracetam comes especially close to fulfilling the desirable pharmacokinetic characteristics for an AED:
(1) it has a high oral bioavailability; (2) it is not significantly bound to plasma proteins; (3) it is eliminated partly in unchanged form by the kidneys and partly by hydrolysis to an inactive metabolite, without involvement of oxidative and conjugative enzymes; (4) it has linear kinetics; and (5) it is not vulnerable to important drug interactions, and(6)Although its half-life is relatively short (6–8 hours), its duration of action is longer than anticipated from its pharmacokinetics
Levetiracetam is probably a major breakthrough in the treatment of epilepsies. It is a highly effective, broad-spectrum, one of second generation AED with a unique mechanism of action.
Chemical structure:
Levetiracetam is a single enantiomer, (S)-α-ethyl-2-oxo-pyrrolidine acetamide. Its molecular formula is C8H14N2O2 and its molecular weight is 170.21. It is chemically unrelated to any of the other antiepileptic drugs. It is a white to off-white powder with a faint odor and bitter taste and highly soluble in water (104.0 g/100 mL). It is freely soluble in chloroform (65.3 g/100 mL) and in methanol (53.6 g/100 mL), soluble in ethanol (16.5 g/100 mL), sparingly soluble in acetonitrile (5.7 g/100 mL) and practically insoluble in …show more content…
Its antiepileptic activity does not involve a direct interaction with any of the other AEDs. In contrast, levetiracetam has been observed to exert several atypical electrophysiological actions, including a moderate inhibition of high voltage-gated N-type Ca2+ channels, reduction of intracellular Ca2+ release from the endoplasmic reticulum, as well as suppression of GABA responses at the GABA-A receptor and glycine-gated currents by blocking its negative allosteric modulation by beta-carbolines and …show more content…
These mice seem normal at birth, but develop unusually severe seizures by 1 or 2 weeks of age and die within 3 weeks after birth.199 Brain membranes and purified synaptic vesicles from mice lacking SV2A did not bind a tritiated derivative of levetiracetam, indicating that SV2A is necessary for levetiracetam binding. Levetiracetam and related derivatives bind to SV2A, but not to the related isoforms SV2B and SV2C expressed in fibroblasts, indicating that SV2A is sufficient for levetiracetam binding. In contrast, none of the other AEDs tested revealed any binding to SV2A. The severe seizures observed in mice lacking SV2A support the interpretation that this protein influences mechanisms of seizure generation or propagation.
Pharmacokinetics
Levetiracetam comes especially close to fulfilling the desirable pharmacokinetic characteristics for an AED:
(1) it has a high oral bioavailability; (2) it is not significantly bound to plasma proteins; (3) it is eliminated partly in unchanged form by the kidneys and partly by hydrolysis to an inactive metabolite, without involvement of oxidative and conjugative enzymes; (4) it has linear kinetics; and (5) it is not vulnerable to important drug interactions, and(6)Although its half-life is relatively short (6–8 hours), its duration of action is longer than anticipated from its pharmacokinetics