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9, Issue 11, 168-176 Review Article ISSN 2454-2229

Soumya et al. World Journal of Pharmaceutical and Life

World Journal Sciences and Life Science
of Pharmaceutical
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CHEMISTRY AND PHARMACOLOGY OF CITICOLINE AND PIRACETAM

COMBINATION IN BRAIN STROKE

Soumya Chakraborty* and Dr Dhrubo Jyoti Sen

School of Pharmacy, Techno India University, Salt Lake City, Sector−V, EM: 4/1, Kolkata−700091, West Bengal,
India.

*Corresponding Author: Soumya Chakraborty

School of Pharmacy, Techno India University, Salt Lake City, Sector−V, EM: 4/1, Kolkata−700091, West Bengal, India.

Article Received on 21/09/2023 Article Revised on 11/10/2023 Article Accepted on 01/11/2023

ABSTRACT
Citicoline+Piracetam is used in the treatment of stroke. It is a combination of two medicines: Citicoline and
Piracetam. Citicoline is a nerve protecting medicine. It works on the brain by nourishing the nerve cells, protects
them from damage and improves their survival. Citicoline and Piracetam is a medication under the branding of
CITCOL−P and is used to treat stroke and mental conditions that can lead to the formation of strokes in a person.
The class of drugs known as nootropics includes piracetam. This kind of medication increases the brain's
cholinergic action. Piracetam is a drug which enhances cognition and memory, slows brain aging, increases oxygen
and blood flow to the brain, improves Alzheimer's and aids in stroke recovery and related conditions. Piracetam
and citicoline stimulate thought without peripheral nervous system stimulation.

KEYWORDS: Ribonucleotide, ischemic attack, phosphatidylcholine, nootropics, NMDA, blood brain barrier.

INTRODUCTION originally used as a drug to help improve memory and

brain function after a stroke.[1] People use citicoline for
Citicoline is a brain chemical that occurs naturally in the
age−related decline in memory and thinking, glaucoma,
body. It's in dietary supplements in the US, but was
stroke, Alzheimer disease, bipolar disorder, depression,
originally a prescription drug in Japan. Citicoline seems
and many other conditions, but there is no good scientific
to increase a brain chemical called phosphatidylcholine.
research to support most of these uses.
Citicoline might also increase the amounts of other
chemicals that send messages in the brain. It was

Figure−1: Citicoline.

Citicoline (Cytidine diphosphate choline): CAS: organic compounds known as pyrimidine ribonucleotide
987−78−0, IUPAC: 5'−O−[hydroxyl diphosphates. These are pyrimidine ribonucleotides with
({hydroxy[2−(trimethylammonio) diphosphate group linked to the ribose moiety. It is
ethoxy]phosphoryl}oxy) phosphoryl]cytidin is iticoline aromatic heteromonocyclic compound. Citicoline is
(INN), also known as cytidine diphosphate−choline naturally occurring in the cells of human and animal
(CDP−Choline) or cytidine 5'−diphosphocholine is an tissue, in particular the organs. Citicoline is available as a
intermediate in the generation of phosphatidylcholine supplement in over 70 countries under a variety of brand
from choline, a common biochemical process in cell names: CereBleu, Cebroton, Ceraxon, Cidilin, Citifar,
membranes.[2] This compound belongs to the class of Cognizin, Difosfocin, Hipercol, NeurAxon, Nicholin,

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 Soumya et al. World Journal of Pharmaceutical and Life Science

Sinkron, Somazina, Synapsine, Startonyl, Trausan, suggest, but have not confirmed, potential benefits of
Xerenoos, etc. When taken as a supplement, citicoline is citicoline for cognitive impairments. Molecular Formula:
hydrolyzed into choline and cytidine in the intestine. [3] C14H27N4O11P2+, Molar Mass: 489.335 g.mol−1.
Once these cross the blood–brain barrier it is reformed Full IUPAC: {2−[({[(2R,3S,4R,5R)−5−(4−amino−2
into citicoline by the rate−limiting enzyme in −oxo−1,2−dihydropyrimidin−1−yl)
phosphatidylcholine synthesis, CTP−phosphocholine −3,4−dihydroxyoxolan−2−yl] methoxy}(hydroxy)
cytidylyltransferase. Memory and cognition studies phosphoryl−phosphono)oxy]ethyl}trimethylazanium.

Formulations:
Dosage form Route Dose Dosage form Route Dose
Injection IM, IV 1000 mg/4ml Injection IM, IV 125 mg/ml
Injection IM, IV 500 mg/4ml Injection, solution IM, IV 1000 mg/ml
Injection, solution IM, IV 1045 mg Injection, solution IM, IV 0.1 g/2ml
Injection, solution IM, IV 522.5 mg Injection, solution IM, IV 1 g/4ml
Tablet Oral 522.500 mg Injection, solution IM, IV 250 mg/2ml

IM: Intramuscular, IV: Intravenous

Citicoline follows Lipinski’s Rule of Five:

Figure−2: Citicoline formulations.

Property:
Water Solubility 7.99 mg/ml logS −1.8 pKa −2.6[basic]
logP −1.4, −7.1 pKa 1.84 [acidic] Charge −1
Hydrogen Acceptor Count 10 Hydrogen Donor Count 4 Polar Area 213.5 Å2
Rotatable Bond 10 Refractivity 113.58m3·mol−1 Polarizibility 42.54 Å3
Number of Rings 2 Bioavailability 1 Rule of Five Yes

Figure−3: Mode of action.

Citicoline has been investigated for the treatment of dementia and Alzheimer disease, cerebrovascular
depression, schizophrenia, stroke, Parkinson disease, disorders), as well as for its ophthalmologic effects. It
brain injury, and cognitive deficits (ie, mild to moderate belongs to the class of other psychostimulants and

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Soumya et al. World Journal of Pharmaceutical and Life Science

nootropics. In summary, citicoline enhances both brain cardiolipin levels in the inner mitochondrial
neuroprotective and neurorepair mechanisms following membrane.[7]
ischemic stroke. Dietary supplementation of citicoline
for 12 wk improved overall memory performance, Cell signalling: Citicoline may enhance cellular
especially episodic memory, in healthy older males and communication by increasing levels of neurotransmitters.
females with AAMI. The findings suggest that regular The choline component of citicoline is used to create
consumption of citicoline may be safe and potentially acetylcholine, which is a neurotransmitter in the human
beneficial against memory loss due to aging.[4] Choline is brain. Clinical trials have found that citicoline
an organic, water−soluble compound. It is neither a supplementation might improve focus and attention.[8]
vitamin nor a mineral. However, it is often grouped with
the vitamin B complex due to its similarities. In fact, this Glutamate transport: Citicoline lowers increased
nutrient affects a number of vital bodily functions. glutamate concentrations and raises decreased ATP
Several studies have shown that Citicoline concentrations induced by ischemia. Citicoline also
supplementation can help enhance attention, focus, and increases glutamate uptake by increasing expression of
concentration. In one study, healthy adult women took EAAT2, a glutamate transporter, in vitro in rat
250−500 mg daily doses of Citicoline for 28 days. The astrocytes. It is suggested that the neuroprotective effects
researchers found that the women experienced of citicoline after a stroke are due in part to citicoline's
significant improvements in attentional performance. ability to decrease levels of glutamate in the brain.[9]
Citicoline contains equimolar amounts of choline and
cytidine. Following citicoline ingestion in rats, the Pharmacokinetics: Citicoline is water−soluble, with
increase in both plasma cytidine and choline occurred more than 90% oral bioavailability. Plasma levels of
quickly, but the molar increase in plasma choline was citicholine peak one hour after oral ingestion, and a
markedly smaller. The half−life of Citicoline is 56 hours majority of the citicoline is excreted as CO2 in
as CO2 and 71 hours in the urine.[5] respiration with the remaining citicoline being excreted
through urine. The pharmacokinetic profile of citicholine
Neuroprotective effects: Citicoline may have cannot be described by a single smooth exponential
neuroprotective effects due to its preservation of decrease over time. However, the elimination half−life
cardiolipin and sphingomyelin, preservation of for citicholine has been reported as approximately 50
arachidonic acid content of phosphatidylcholine and hours for citicholine removed via respiration and
phosphatidylethanolamine, partial restoration of approximately 70 hours for citicholine removed via
phosphatidylcholine levels, and stimulation of urine. Plasma levels of choline peak about four hours
glutathione synthesis and glutathione reductase activity. after ingestion.[10]
Citicoline's effects may also be explained by the
reduction of phospholipase A2 activity. Citicoline Side effects: Citicoline has a very low toxicity profile in
increases phosphatidylcholine synthesis. The mechanism animals and humans. Clinically, doses of 2000 mg per
for this may be: day have been observed and approved. Minor transient
adverse effects are rare and most commonly include
By converting 1, 2−diacylglycerol into stomach pain and diarrhea. There have been suggestions
phosphatidylcholine that chronic citicoline use may have adverse psychiatric
effects. However, a meta−analysis of the relevant
Stimulating the synthesis of SAMe, which aids in literature does not support this hypothesis. At most,
membrane stabilization and reduces levels of arachidonic citicoline may exacerbate psychotic episodes or interact
acid. This is especially important after an ischemia when with antipsychotic medication.[11]
arachidonic acid levels are elevated.[6]
Piracetam [CAS: 7491−74−9; IUPAC:
Neuronal membrane: The brain preferentially uses 2−(2−Oxopyrrolidin−1−yl)acetamide] is a drug marketed
choline to synthesize acetylcholine. This limits the as a treatment for myoclonus. Molecular Formula:
amount of choline available to synthesize C6H10N2O2. Molar mass: 142.158 g·mol −1. It is also used
phosphatidylcholine. When the availability of choline is as a cognitive enhancer to improve memory, attention,
low or the need for acetylcholine increases, and learning. Evidence to support its use is unclear, with
phospholipids containing choline can be catabolized some studies showing modest benefits in specific
from neuronal membranes. These phospholipids include populations and others showing minimal or no benefit.
sphingomyelin and phosphatidylcholine. Piracetam is sold as a medication in many European
Supplementation with citicoline can increase the amount countries. Sale of piracetam is not illegal in the United
of choline available for acetylcholine synthesis and aid in States, although it is not regulated nor approved by the
rebuilding membrane phospholipid stores after depletion. FDA so it is legally sold for research use only.[12]
Citicoline decreases phospholipase stimulation. This can Piracetam is in the racetams group, with chemical name
lower levels of hydroxyl radicals produced after an 2−oxo−1−pyrrolidine acetamide. It is a cyclic derivative
ischemia and prevent cardiolipin from being catabolized of the neurotransmitter GABA and shares the same
by phospholipase A2. It can also work to restore 2−oxo−pyrrolidone base structure with pyroglutamic

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Soumya et al. World Journal of Pharmaceutical and Life Science

acid. Related drugs include the anticonvulsants of action differ from that of endogenous GABA.
levetiracetam and brivaracetam, and the putative Piracetam has neuroprotective and anticonvulsant
nootropics aniracetam and phenylpiracetam.[13] properties and is reported to improve neural plasticity. Its
Piracetam is a nootropic cyclic GABA derivative used in efficacy is documented in cognitive disorders and
myoclonus, sickle cell disease, alcohol dependence, and dementia, vertigo, cortical myoclonus, dyslexia, and
as a general cognitive enhancer. Piracetam is a nootropic sickle cell anemia although the clinical application in
drug in the racetams group, with chemical name these conditions is not yet established. Piracetam has
2−oxo−1−pyrrolidine acetamide. It shares the same effects on the vascular system by reducing erythrocyte
2−oxo−pyrrolidone base structure with pyroglutamic adhesion to the vascular endothelium, hindering
acid and is a cyclic derivative of the neurotransmitter vasospasms and facilitating microcirculation.[14]
γ−aminobutyric acid (GABA). However its mechanism

Figure−4: Piracetam.

Pharmacodynamics: Piracetam is known to mediate human studies, the cognitive processses including
various pharmacodynamic actions. learning, memory, attention and consciousness were
enhanced from piracetam therapy without inducing
Neuronal effects: Piracetam modulates the cholinergic, sedation and psychostimulant effects. Piracetam mediate
serotonergic, noradrenergic, and glutamatergic neuroprotective effects against hypoxia−induced
neurotransmission although the drug does not display damage, intoxication, and electroconvulsive therapy.[16]
high affinity to any of the associated receptors (Ki In two studies involving alcohol−treated rats with
>10μM). Instead, piracetam increases the density of evidences of withdrawal−related neuronal loss,
postsynaptic receptors and/or restore the function of piracetam was shown to reduce the extent of neuronal
these receptors through stabilizing the membrane fluidity loss and increase the numbers of synapses in the
1. In the forebrain of aging mice, the density of NMDA hippocampus by up to 20% relative to alcohol−treated or
[N−methyl−D−aspartate] receptors was increased by alcohol−withdrawn rats. This suggests that piracetam is
approximately 20% following 14 days of piracetam capable in promoting neuroplasticity when recoverable
treatment. The N−methyl−D−aspartate (NMDA) neural circuits are present. Although the mechanism of
receptor is a receptor of glutamate, the primary action is not fully understood, administration of
excitatory neurotransmitter in the human brain.[15] It piracetam prior to a convulsant stimulus reduces the
plays an integral role in synaptic plasticity, which is a seizure severity and enhances the anticonvulsant
neuronal mechanism believed to be the basis of memory effectiveness of conventional antiepileptics such as
formation. Based on the findings of various animal and carbamazepine and diazepam.[17]

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Soumya et al. World Journal of Pharmaceutical and Life Science

Figure−5: Brain Stroke.

Stroke is a medical condition in which poor blood flow stroke rehabilitation, and ideally takes place in a stroke
to the brain causes cell death. There are two main types unit; however, these are not available in much of the
of stroke: ischemic, due to lack of blood flow, and world.
hemorrhagic, due to bleeding. Both cause parts of the
brain to stop functioning properly. Signs and symptoms In 2013, approximately 6.9 million people had ischemic
of stroke may include an inability to move or feel on one stroke and 3.4 million people had hemorrhagic stroke. In
side of the body, problems understanding or speaking, 2015, there were about 42.4 million people who had
dizziness, or loss of vision to one side. Signs and previously had stroke and were still alive. Between 1990
symptoms often appear soon after the stroke has and 2010 the annual incidence of stroke decreased by
occurred. If symptoms last less than one or two hours, approximately 10% in the developed world, but
the stroke is a transient ischemic attack (TIA), also called increased by 10% in the developing world. In 2015,
a mini−stroke. Hemorrhagic stroke may also be stroke was the second most frequent cause of death after
associated with a severe headache. The symptoms of coronary artery disease, accounting for 6.3 million deaths
stroke can be permanent. Long−term complications may (11% of the total). About 3.0 million deaths resulted
include pneumonia and loss of bladder control. The from ischemic stroke while 3.3 million deaths resulted
biggest risk factor for stroke is high blood pressure. from hemorrhagic stroke. About half of people who have
Other risk factors include high blood cholesterol, tobacco had stroke live less than one year. Overall, two thirds of
smoking, obesity, diabetes mellitus, a previous TIA, cases of stroke occurred in those over 65 years old. There
end−stage kidney disease, and atrial fibrillation. are two main causes of stroke: a blocked artery (ischemic
Ischemic stroke is typically caused by blockage of a stroke) or leaking or bursting of a blood vessel
blood vessel, though there are also less common causes. (hemorrhagic stroke). Some people may have only a
Hemorrhagic stroke is caused by either bleeding directly temporary disruption of blood flow to the brain, known
into the brain or into the space between the brain's as a transient ischemic attack (TIA), that doesn't cause
membranes. Bleeding may occur due to a ruptured brain lasting symptoms. A stroke, sometimes called a brain
aneurysm. Diagnosis is typically based on a physical attack, occurs when something blocks blood supply to
exam and supported by medical imaging such as a CT part of the brain or when a blood vessel in the brain
scan or MRI scan. A CT scan can rule out bleeding, but bursts. In either case, parts of the brain become damaged
may not necessarily rule out ischemia, which early on or die. A stroke can cause lasting brain damage,
typically does not show up on a CT scan. Other tests long−term disability, or even death. A stroke happens
such as an electrocardiogram (ECG) and blood tests are when blood flow to any part of the brain stops. Each
done to determine risk factors and rule out other possible person has a different recovery time and need for
causes. Low blood sugar may cause similar symptoms. long−term care. Problems with moving, thinking, and
talking often improve in the first weeks or months after a
Prevention includes decreasing risk factors, surgery to stroke. Some people will keep improving months or
open up the arteries to the brain in those with years after a stroke. Signs of a TIA or stroke may
problematic carotid narrowing, and warfarin in people include:
with atrial fibrillation. Aspirin or statins may be
recommended by physicians for prevention. Stroke or Sudden confusion, trouble speaking, or trouble
TIA often requires emergency care. Ischemic stroke, if understanding speech.
detected within three to four−and−a−half hours, may be Sudden numbness or weakness, especially on one side of
treatable with a medication that can break down the clot. the body.
Some cases of hemorrhagic stroke benefit from surgery. Sudden severe headache with no known cause.
Treatment to attempt recovery of lost function is called Sudden trouble seeing from one or both eyes.

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Soumya et al. World Journal of Pharmaceutical and Life Science

Figure−6: Piracetam Formulations.

Vascular effects: Piracetam is shown to increase the platelet membranes. At the vascular level, piracetam
deformability of erythrocytes, reduce platelet decreases adhesion of erythrocytes to cell wall and
aggregation in a dose−dependent manner, reduce the reduces vasospasm which in turn improves
adhesion of erythrocytes to vascular endothelium and microcirculation including cerebral and renal blood
capillary vasospasm. In healthy volunteers, piracetam flow.[19]
mediated a direct stimulant effect on prostacycline
synthesis and reduced the plasma levels of fibrinogen Absorption: Piracetam displays a linear and
and von Willebrand’s factors (VIII: C; VIII R: AG; VIII time−dependent pharmacokinetic properties with low
R: vW) by 30 to 40%. Potentiated microcirculation is intersubject variability over a large range of doses.
thought to arise from a combination of effects on Piracetam is rapidly and extensively absorbed following
erythrocytes, blood vessels and blood coagulation.[18] oral administration with the peak plasma concentration is
reached within 1 hour after dosing in fasted subjects.
Mechanism of action: Half Life: 4−5 hours. Piracetam Following a single oral dose of 3.2 g piracetam, the peak
interacts with the polar heads in the phospholipids plasma concentration (Cmax) was 84 µg/mL. Intake of
membrane and the resulting mobile drug−lipid food may decrease the Cmax by 17% and increase the
complexes are thought to reorganize the lipids and time to reach Cmax (Tmax) from 1 to 1.5 hours. Tmax in
influence membrane function and fluidity. Such the cerebrospinal fluid is achieved approximately 5 hours
interaction has been reported in a study that investigated post−administration. The absolute bioavailability of
the effects of neuronal outgrowth induced by beta piracetam oral formulations is close to 100% and the
amyloid peptides; while amyloid peptides cause lipid steady state plasma concentrations are achieved within 3
disorganization within the cell membranes leading to days of dosing.[20]
neuronal death, piracetam demonstrated to decrease the
destabilizing effects of amyloid peptide. The authors Volume of distribution: Vd is approximately 0.6L/kg.
suggest that piracetam induces a positive curvature of the Piracetam may cross the blood−brain barrier as it was
membrane by occupying the polar groups in the measured in the cerebrospinal fluid following
phospholipids to counteract the negative curvature intravenous administration. Piracetam diffuses to all
induced by amyloid peptides, which in turn would tissues except adipose tissues, crosses placental barrier
decrease the likelihood of membrane fusion. This and penetrates the membranes of isolated red blood cells.
mechanism of action is thought to improve membrane
stability, allowing the membrane and transmembrane Protein binding: Piracetam is not reported to be bound
proteins to maintain and recover the three−dimensional to plasma proteins.
structure or folding for normal function 4 such as
membrane transport, chemical secretion, and receptor Metabolism: As large proportion of total piracetam
binding and stimulation. Through restored membrane administered is excreted as unchanged drug, there is no
fluidity, piracetam promotes restored neurotransmission known major metabolism of piracetam.[21]
such as glutamatergic and cholinergic systems, enhances
neuroplasticity and mediates neuroprotective and Route of elimination: Piracetam is predominantly
anticonvulsant effects at the neuronal level. It is also excreted via renal elimination, where about 80−100% of
demonstrated that piracetam also improves the fluidity of the total dose is recovered in the urine. Approximately

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Soumya et al. World Journal of Pharmaceutical and Life Science

90% of the dose of piracetam is excreted in the urine as hyperkinesia, weight gain, nervousness, somnolence,
unchanged drug. depression and asthenia. Piracetam reduces platelet
aggregation as well as fibrinogen concentration, and thus
Half−life: The plasma half−life of piracetam is is contraindicated to patients with cerebral
approximately 5 hours following oral or intravenous haemorrhage.[22]
administration. The half life in the cerebrospinal fluid
was 8.5 hours. Side effects: Symptoms of general Clearance: The apparent total body clearance is 80−90
excitability, including anxiety, insomnia, irritability, mL/min. Toxicity: The LD50 for oral consumption in
headache, agitation, nervousness, tremor, and humans has not been determined. The LD50 is 5.6 g/kg
hyperkinesia, are occasionally reported. Other reported for rats and 20 g/kg for mice, indicating extremely low
side effects include somnolence, weight gain, clinical acute toxicity. For comparison, in rats the LD50 of
depression, weakness, increased libido, and vitamin C is 12 g/kg and the LD50 of table salt is 3
hypersexuality. According to a 2005 review, piracetam g/kg.[23]
has been observed to have the following side effects:

Figure−7: Citicoline and Piracetam combination formulation.

Adverse Effects: Improve decision support & research extreme high dose of sorbitol contained in the used
outcomes. With structured adverse effects data, formulation. In cases of acute, significant over dosage,
including: blackbox warnings, adverse reactions, stomach emptying by gastric lavage or induced emesis is
warning & precautions, & incidence rates.[24] recommended as there are no known antidotes for
piracetam. Management for an overdose will most likely
Toxicity: The cases of overdose with piracetam is rare. be symptomatic treatment and may include hemodialysis,
The highest reported overdose with piracetam was oral where the extraction efficacy of the dialyser is 50 to 60%
intake of 75g which was associated with diarrhea and for the drug. Oral LD50 in a mouse acute toxicity study
abdominal pain; the signs were most likely related to the was 2000 mg/kg MSDS.[25]

Property
State Solid Melting Point 152°C Boiling point Decomposes
Water Solubility 479.0 mg/ml logS 0.53 pKa −2 [basic]
logP −1.6, −1.7 pKa 15.93 [acidic] Charge 0
Hydrogen Acceptor Count 2 Hydrogen Donor Count 1 Polar Area 63.4 Å2
Rotatable Bond 2 Refractivity 35.06 m3·mol−1 Polarizibility 13.96 Å3
Number of Rings 1 Bioavailability 1 Rule of Five Yes

Mechanisms of action: Piracetam's mechanism of memory processes. Furthermore, piracetam may have an
action, as with racetams in general, is not fully effect on NMDA glutamate receptors, which are
understood. The drug influences neuronal and vascular involved with learning and memory processes. Piracetam
functions and influences cognitive function without is thought to increase cell membrane permeability.
acting as a sedative or stimulant. Piracetam is a positive Piracetam may exert its global effect on brain
allosteric modulator of the AMPA receptor, although this neurotransmission via modulation of ion channels (i.e.,
action is very weak and its clinical effects may not Na+, K+). It has been found to increase oxygen
necessarily be mediated by this action. It is hypothesized consumption in the brain, apparently in connection to
to act on ion channels or ion carriers, thus leading to ATP metabolism, and increases the activity of adenylate
increased neuron excitability.[26] GABA brain kinase in rat brains. Piracetam, while in the brain,
metabolism and GABA receptors are not affected by appears to increase the synthesis of cytochrome b5,
piracetam. Piracetam improves the function of the which is a part of the electron transport mechanism in
neurotransmitter acetylcholine via muscarinic mitochondria. But in the brain, it also increases the
cholinergic (ACh) receptors, which are implicated in permeability of some intermediates of the Krebs cycle

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Soumya et al. World Journal of Pharmaceutical and Life Science

through the mitochondrial outer membrane. Piracetam 8. Grau M, Montero JL, Balasch J, "Effect of
inhibits N−type calcium channels. The concentration of Piracetam on electrocardiogram and local cerebral
piracetam achieved in central nervous system after a glucose utilization in the rat". General
typical dose of 1200 mg (about 100 μM) is much higher pharmacology, 1987; 18(2): 205–11.
than the concentration necessary to inhibit N−type 9. Winnicka K, Tomasiak M, Bielawska A,
calcium channels (IC50 of piracetam in rat neurons was "Piracetam−−an old drug with novel properties".
3 μM).[27] Acta poloniae pharmaceutica, 2005; 62(5): 405–9.
10. D’Orlando KJ, Sandage BW Jr, Citicoline
CONCLUSION (CDPcholine): mechanisms of action and effects in
ischemic brain injury. Neurol Res, 1995; 17:
Memory impairment and enhancement of cognitive
281−284.
function of brain is a part of treatment of various
11. Jordaan, B, Oliver, DW, Dormehl, IC, Hugo, N.
disorders associated with elderly patients or patients with
"Cerebral blood flow effects of piracetam,
neurological disorders at any age due to stroke and
pentifylline, and nicotinic acid in the baboon model
related shocks. Nutraceuticals are effective ways of
compared with the known effect of acetazolamide".
treating such conditions. Various drugs are identified and
Arzneimittel−Forschung, 1996; 46(9): 844–7.
established as therapeutic agents for treatment of
12. Paula−Barbosa, MM; Brandão, F; Pinho, MC;
cognitive disorders. Effective therapy can be set forth if
Andrade, JP; Madeira, MD; Cadete−Leite, A "The
rationale combinations of such agents are being design,
effects of piracetam on lipofuscin of the rat cerebella
characterized for their pharmacological, biochemical and
and hippocampus neurons after long−term alcohol
physical compatibility and developed into suitable
treatment and withdrawal: a quantitative study".
formulation. Nutraceutical combinations are coming into
Alcoholism, clinical and experimental research,
the market as boost for health care system to prevent
1991; 15(5): 834–8.
early degeneration of neurons, memory loss and brain
13. Secades JJ, Frontera G, CDP−choline:
related aging. Citicoline and piracetam is one of such
pharmacological and clinical review. Methods Find
combination which has been proved pharmacologically,
Exp Clin Pharmacol, 1995; 17: 1−54.
biochemically and physically compatible. It has been
14. Voet Judith G, Voet Donald, Biochemistry. New
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15. B. Pathan et al: Asian Journal of Biomedical and
alcoholism, clotting, coagulation, vasospastic disorders
Pharmaceutical Sciences, 2012; 2(12): 15−20.
alzheimer’s and senile dementia, depression and anxiety
16. Skondia, V, Kabes, J. "Piracetam in alcoholic
stroke, ischemia and symptoms, dyspraxia and
psychoses: a double−blind, crossover, placebo
dysgraphia, closed craniocerebral trauma.
controlled study". The Journal of international
medical research, 1985; 13(3): 185–7.
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