Levetiracetam

Anticonvulsants Central Nervous System Depressants

Indication

Used as adjunctive therapy in the treatment of partial onset seizures in adults and children 4 years of
age and older with epilepsy.

Structured Indications

 Grand mal Generalized tonic-clonic seizure

 Myoclonic seizures
 Partial onset seizure Epilepsy
 Refractory seizure disorders

Mechanism of action

Protection was observed, however, against secondarily generalized activity from focal seizures
induced by pilocarpine and kainic acid, two chemoconvulsants that induce seizures that mimic some
features of human complex partial seizures with secondary generalization. Levetiracetam also displayed
inhibitory properties in the kindling model in rats, another model of human complex partial seizures,
both during kindling development and in the fully kindled state. The predictive value of these animal
models for specific types of human epilepsy is uncertain. Levetiracetam is thought to stimulate synaptic
vesicle protein 2A (SV2A), inhibiting neurotransmitter release. (ENHANCEMENT OF SYNAPTIC
INHIBITION-INCREASE GABA)
 Cerebrolysin is the drug which contains peptides derived from the brain of a pig. It is used
in neurological practice for recovery of stroke patients and treatment of dementia. Despite the
evidence-basis and some experimental studies, the distinct mechanisms of pharmacological action of
this drug remain unclear for most neurologists. In this paper, we present results of a molecular-
biological analysis of peptide content of cerebrolysin. We have demonstrated the presence of active
peptide fragments of nerve growth factor, enkephalins, orexin, halanin. The results of current clinical
and experimental studies of cerebrolysin have been compared. The activity of above-mentioned
neuropeptides explain experimental and clinical details of all known effects (neurotrophic,
neuroprotective and immunomodulating) of cerebrolysin in ischemic and neurodegenerative CNS
injuries. The analysis allowed to make conclusions about mechanisms of cerebrolysin action that were
important for increasing the efficacy of this drug in clinical practice.

MECHANISM OF ACTION AND PHARMACOLOGICAL EFFECTS

Since Cerebrolysin is a mixture of various peptides and amino acids, its exact pharmacology is
still not clear. Each neuropeptide has its function. Here is the information I was able to get about how it
works:

Protection of neurons against damaging conditions (Neuroprotective action). The drug prevents
the formation of free radicals and decreases the concentration of lipid peroxides. Suppress glutamate
excitotoxicity (is the pathological process by which neurons are damaged and killed by the
overactivations of receptors for the excitatory neurotransmitter glutamate, such as the NMDA receptor
and AMPA receptor) and prevents neuronal death caused by ischemia and hypoxia.

Metabolic regulations. This includes improvement of brain energy metabolism and intracellular
protein synthesis.

Neurotrophic activity, which is similar to natural nerve growth factors by its action. Cerebrolysin
stimulates neuronal differentiation and sprouting, supports the survival of neurons. In the experimental
model of Alzheimer’s, it was shown to slow down the process of neurodegeneration.

Neuromodulatory effects include restoration of impaired cognitive functions, improvement of

concentration and the processes of memorization and the recall of memory. This nootropic also has a
positive effect on the mood.

Acetylcysteine protects against acetaminophen overdose-induced hepatotoxicity by

maintaining or restoring hepatic concentrations of glutathione. It does this by producing the glutathione
precursor L-cysteine. Glutathione is required to inactivate an intermediate metabolite (N-acetyl-p-
benzoquinoneimine or NAPQI) of acetaminophen that is thought to be hepatotoxic. In acetaminophen
overdose cases, excessive quantities of this metabolite are formed because the primary metabolic
(glucuronide and sulfate conjugation) pathways become saturated. Acetylcysteine may act by reducing
the metabolite to the parent compound and/or by providing sulfhydryl for conjugation of the
metabolite. Experimental evidence also suggests that a sulfhydryl-containing compound such as
acetylcysteine may also directly inactivate the metabolite. The mechanisms of action for acetylcysteine’s
well-known mucolytic effects are different. In particular, when inhaled, acetylcysteine (and its metabolic
byproduct cysteine) exerts its mucolytic action through its free sulfhydryl group, which reduces the
disulfide bonds in the mucus matrix and lowers mucus viscosity. This action increases with increasing pH
and is most significant at pH 7 to 9. The mucolytic action of acetylcysteine is not affected by the
presence of DNA. Acetylcysteine is also an antioxidant and reduces oxidative stress. Acetylcysteine
serves as a prodrug to L-cysteine which is a precursor to the biologic antioxidant, glutathione and hence
administration of acetylcysteine replenishes glutathione stores. L-cysteine also serves as a precursor to
cystine which in turn serves as a substrate for the cystine-glutamate antiporter on astrocytes hence
increasing glutamate release into the extracellular space. This glutamate in turn acts on mGluR2/3
receptors, and at higher doses of acetylcysteine, mGluR5. Glutathione also modulates the NMDA
receptor by acting at the redox site. These effects on glutamate and NMDA signaling appear to explain
some of the positive neuropsychotropic effects associated with NAC. Acetylcysteine also possesses some
anti-inflammatory effects possibly via inhibiting NF-κB through redox activation of the nuclear factor
kappa kinases thereby modulating cytokine synthesis.

Piracetam boosts brain health and function in several ways. But two in particular stand out.
Piracetam modulates AMPA and NMDA receptors in the brain. And improves the flow of acetylcholine
(ACh) and sensitivity and density of ACh receptors.[ix]

This German study conducted with lab mice showed Piracetam elevated NMDA receptor
density. And normalized the way those receptors worked with L-Glutamate similar to that of a healthy
brain.

Deficits at the level of NMDA receptors could be one of the mechanisms of action underlying
age-related cognitive decline. And the researchers concluded that Piracetam showed cognition-
enhancing properties.[x]

This effect on NMDA receptor sites is directly related to our interest in using Piracetam for Long-
Term Potentiation and the support of long-term memory formation.

Neuroplasticity is dependent on activation of NMDA receptors.[xi] And this neuroplasticity is at

the heart of memory formation. Reviews of Piracetam used by neurohackers frequently report the
return of long-lost memories. Further proof of the efficacy in using Piracetam to support learning and
memory.

Piracetam increases cerebral blood flow. Several studies have shown how Piracetam positively
influences brain blood flow. Cerebral blood flow is critical for the highly optimized brain. Blood delivers
oxygen and glucose needed for cellular metabolism, and helps carry away cellular waste.[xii]

Strokes can be caused by an interruption in cerebral blood flow. Starving parts of the brain of
oxygen and glucose. This double-blind, placebo-controlled study was done with 24 stroke patients. One
group received 2,400 mg of Piracetam twice daily, and the other a placebo.

Before treatment, both groups were comparable in performance during language tasks. The
study found that Piracetam improved recovery of various language functions. And this effect was
attributed to increased blood circulation to areas of the brain related to language. The placebo group
showed very little improvement in areas of language.[xiii]