Report on CNS Pharmacology: Carbamazepine & Piperazine Effects

This report provides a comprehensive overview of the pharmacology of central nervous system (CNS) drugs, specifically focusing on Carbamazepine, an anti-epileptic drug, and Piperazine, an anti-psychotic drug. The introduction establishes the role of the CNS and the effects of drugs on its function. The report is divided into two summaries tailored for different audiences: a general public summary and a scientific audience summary. The first summary explains the mechanisms of action, uses, and side effects of both drugs in accessible language. The second summary delves deeper into the detailed mechanisms of action, pharmacokinetics (absorption, distribution, metabolism, and elimination), receptor activation, and contraindications of each drug, providing a more in-depth analysis. The report concludes by summarizing the key aspects of both drugs and highlighting the importance of understanding their pharmacology to minimize adverse drug interactions and optimize patient outcomes. The report also includes references to support the information presented.

CNS Pharmacology Drugs Portfolio

Table of Contents
INTRODUCTION................................................................................................................................3
Summary 1: For general public ......................................................................................................3
Summary 2: for a scientific audience..............................................................................................6
CONCLUSION....................................................................................................................................9
REFERENCES...................................................................................................................................10

INTRODUCTION
Central nervous system is regarded as the system which directs the functioning of overall
tissues present in body. On the other hand, peripheral nervous system acts by receiving numerous
sensory signals and helps in transmitting them to brain through spinal cord. As soon as a drug is
incorporated in body, the brain processes the incoming information and discards all the unwanted
information received by brain (Adams and Carol 2015). After the signals are evaluated, the
receptors of the brain initiate neural impulses to produce appropriate response of drugs on the
organs and tissues.
The report will study the pharmacological actions of anti-epileptic and anti-psychotic drugs
on central nervous system of the body. The study will comprise of two summaries based on general
audience and scientific audience. It will focus on different aspects of drugs such as mechanism of
actions, different receptors and side effects of particular drugs acting on central nervous system.
Summary 1: For general public
1. Anti-epileptic drug- Carbamazepine: This is one of the anti-epileptic drugs used to treat
epileptic disorders which arises due to improper functioning and imbalance between
neurotransmission, glutamate actions and inhibitory neurotransmission which is facilitated by
Gamma-Aminobutyric Acid (GABA) (Alexander, Benson and Harmar, 2013). Anti-epileptic drugs
usually act by blocking the depolarizing ion channels or by decreasing the action of
neurotransmitters.
Mechanism of action of Carbamazepine
 Carbamazepine mainly functions by blocking the Na+ channels during the process of
depolarization. Blocking helps in controlling the excitability of neural cells which causes
epileptic seizures (Daniel, Chau and Haucke, 2015).
 It gradually decreases the neuronal firing which takes place in brain.
 It reduces the transmission of brain impulses which differ from normal impulses. It also acts by decreasing the activity of glutamine acid which is responsible for excitement
of nerve impulses.
Where do Carbamazepine acts?
It acts on central nervous system by preventing the abnormal transmission of electrical
signals across the brain (Devaraneni, Zhou and Shyng, 2014).
How does Carbamazepine acts?
Brain consists of millions of nerve cells that unite to form central nervous system which is
responsible for conducting and communicating electrical signals. If the nerve signals are not
regulated properly, it shows abnormality which results in seizures (Hilal-Dandan and Brunton,

2013). Carbamazepine acts by preventing sodium gated channels to build up in brain. This helps in
stabilizing the neural transmission across the brain.
What is Carbamazepine mainly used to treat?
It is generally used to treat focal seizures and primary tonic clonic seizures. It is reported to
worsen the condition of myoclonic seizures (Nicosia, Giordano and Tantucci, 2015).
Contraindications of Carbamazepine
 This drug is contraindicated in individuals with history of heart blockage and
atrioventricular disorders.
 People with decreased level of red and white blood corpuscles are not prescribed with
Carbamazepine.
 It is not suggested for patients suffering from glaucoma. Carbamazepine is should not be taken along with other herbal and complementary
medicines (O’Mahony and Hodnett, 2013).
Doses of Carbamazepine for children and adults
1. Adults: 800mg-1200mg divided into 4 doses, which contributes to 200mg-300mg per dose.
2. Children: 1 month- 12 years: 5mg/kg up to 3 doses in a day. Children above 12 years can be
given 200mg-400mg three times a day (Sharma, Singh and Mathew, 2015).
Possible side-effects of Carbamazepine
 Sleepiness
 Dizziness
 Feeling of nausea and vomiting sensations
 Decrease in levels of red and white cell corpuscles resulting in leukaemia and leucopenia.
 Blurred vision.
 Rectal and anal irritation in many cases (Sun, Zeng and Lemley, 2013).
 Visual and auditory hallucination in rare cases. Severe fluctuation in blood pressure levels.
2. Anti-psychotic drug- Piperazine: Piperazine is classified as six member carbon compound
containing two nitrogen atoms at the opposite end of the ring. It was originally named because it
showed resemblance with piperidine which is a part of chemical structure of piperine (Bolles,
Fujiwara and Furge, 2014). It was initially introduced in the field of medicines as anthelmintics to
paralyse the parasites in the host body.
Mechanism of action of Piperazine
 The imidazothiazole anti-helmintics acts as agonist on nicotine acetylcholine receptors of
nematodes (Chen, Wang and Zhang, 2013).
 Their anthelmintics mainly act on the ganglion receptors to stimulate ganglion-like

structures in somatic muscle cells of nematodes.
 These stimulations further results in sustained muscle contractions which is followed by
neuromuscular depolarization. Piperazine acts by blocking the neuromuscular transmission in parasites during the hyper-
polarization process (Chen, Zhao and Xu, 2012).
Where does Piperazine acts?
Piperazine usually acts on the muscular cells of Ascaris nematode. It functions by expelling
the worms from the host body which makes them motionless and relaxed (Chitra, Babitha and
Badami, 2014). Piperazine do not kill those nematodes, they can revive again in Ringer solution at
37º C.
How does Piperazine acts?
It acts by increasing the average resting potential above 40mV which further decreases the
activity of pacemaker in heart. The introduction of Piperazine results in rapid hyper-polarization
which is required to paralyse the muscles cells of Ascaris present in the host body (Johnstone,
Reierson and Bixby, 2012).
What is Piperazine mainly used to treat?
Piperazine is mainly used to treat infections produced due to common roundworms such as
Ascaris (Owens, 2014). It is most commonly used anti-psychotic drug because it produces least
sedation and is highly potent in its activity.
Contraindications of Piperazine
 Intake of Piperazine should be stopped during pregnancy because it can lead to
malformations in the first-trimester of pregnancy.
 It should be used with caution in children because of the increased chances of neurotoxicity
(Silva, Schuck and Gnoatto, 2015).
 Piperazine should not be taken along with drugs such as chlorpromazine and
phenothioazines due to increased risk of seizures. Hepatic dysfunction and renal disorders occurs due to Piperazine.
Doses of Piperazine in Children and adults
1. Adults: 2gms three times a day.
2. Children: 2-8 years- 2gms once in a day
8-14 years- 2gms twice in a day.
Possible side-effects of Piperazine
 Double or unclear vision
 Clumsiness
 Severe skin irritation and rashes

 Rise in body temperature
 Laryngitis.
 Muscular and joint pains.
Summary 2: for a scientific audience
1. Anti-epileptic drug: Carbamazepine.
Detailed Mechanism of Carbamazepine
 The main action of Carbamazepine is to stabilise the hyper-excitation of nerve membranes
present in brain. It inhibits the repetitive neuronal discharge which further decreases the
synaptic transmission of excitatory impulses (Alexander, Benson and Harmar, 2013).
 The drug mainly functions by preventing the repetitive firing of sodium mediated channels
in the depolarised state of neurons.
 Further it also possess the anti-cholinergic and anti-diuretic activity which reduces the
depressant effect in body.
Pharmacokinetics of Carbamazepine.
1. Absorption: The absorption of Carbamazepine is very slow in the gastrointestinal tract but it
is complete in conventional forms of tablet. When Carbamazepine is administered orally it
produces the peak concentration of unchanged drug in the 4-10 hours (O’Mahony and
Hodnett, 2013).
2. Distribution: The concentration of unchanged Carbamazepine variates between 20-30% as
compared to plasma concentrations Relatively higher concentration of milk is observed
which constitute from 25-60% (Nicosia, Giordano and Tantucci, 2015). Carbamazepine
effectively crosses the placental barrier and readily gets distributed with volume of 0.8 to 1.9
L/kg.
3. Metabolism: Carbamazepine is metabolised in liver through epoxide-diol pathways. The
main by product of Carbamazepine is (Carbamazepine -10, 11-epoxide) which is active
pharmacologically (Daniel, Chau and Haucke, 2015).
4. Elimination: The half-life of this drug following a single dose varies from 28-36 hours.
Whereas repeated dose produce hepatic enzyme induction by decreasing the half life of the
drug from 16-24 hours. 74% of 400 mg Carbamazepine is excreted through urine in the form
of hydroxylated metabolites (Hilal-Dandan and Brunton, 2013). Remaining 26% of the drug
is excreted through faecal matter.
Receptor activation mechanism of Carbamazepine

 Carbamazepine interacts with wide variety of channels and receptors to target the voltage
gated sodium ion channels
 Carbamazepine-epoxide relatively slow downs the rate of neuronal firing which is caused in
central nervous system.
 It was found that Carbamazepine blocks [3H]batrachotoxin or [3H]ba-trachotoxinin A 20-
alpha benzoate binding to synapto-somes (Alexander, Benson and Harmar, 2013).
 The effect is more prominently observed during the depolarizing stage of nerve cells. It
inhibits the sodium influx during electrical signal transmission which is responsible for
seizures and neuronal disorders.
Toxicity and Contraindications
 Mild skin irritation persists within few weeks of administration of Carbamazepine.
 Hypersensitivity is seen in patients which can lead to delayed multi-organ disorder and high
fever (Daniel, Chau and Haucke, 2015).
 It also causes severe hepatic and renal failure in patients with liver dysfunction and renal
calculi.
 Carbamazepine tends to reduce the serum level in individuals with hypothyroidism. Patients
may require thyroid replacement therapy to balance the thyroid concentration in body.
2. Anti-psychotic drug: Piperazine
Detailed Mechanism of Piperazine
This drug is a class of organic compound containing Piperazine rings in it. The drug exhibits its
action due to the presence of saturated aliphatic six member heterocyclic ring with a set of nitrogen
attached on opposite sides of carbon atoms (Bolles, Fujiwara and Furge, 2014).
It is a Gamma-Amino Butyric Acid receptor agonist which have the property of binding directly to
the GABA receptors. It acts by producing hyper polarization in nerve endings of neurons.
This causes paralysis of the worms which makes them motionless, narcotised and relaxed but
Piperazine do not have the ability to kill the worms (Chen, Wang and Zhang, 2013).
Pharmacokinetics of Piperazine
1. Absorption: The pharmacokinetic behaviour of Piperazine resembles to all the salts and
derivatives of Piperazine. It is usually administered orally which is readily absorbed in blood
through gastrointestinal tract (Johnstone, Reierson and Bixby, 2012).

2. Distribution: 65% of protein binding takes place in Piperazine with no blood or plasma
partitioning ratio (Bolles, Fujiwara and Furge, 2014).
3. Metabolism: It has been observed that 25% of Piperazine is metabolised in liver. Nitration
of Piperazine is necessary to convert it into N -mononitrosopiperazine (MNPz) so that it is
readily metabolised in liver with the help of gastric and other juices (Chitra, Babitha and
Badami, 2014).
4. Elimination: The excretion and elimination of Piperazine is very fast. It is detected in half
an hour after the oral administration of drug. It is usually eliminated through urine.
Receptor activation mechanism of Piperazine
 Piperazine mainly acts by blocking the transmission of nerve cells by hyper-polarizing the
nerve membrane.
 This results in opening of the chlorine mediated channels, hence, allowing an influx of
chloride ions. Different chloride channel subunits produces variable sensitivity to macro-
cyclic lactones and different sites of expression (Chen, Wang and Zhang, 2013).
 It effects the paralysis of neuromuscular membranes of nematodes at various sites such as
body wall linings, uterine muscles and gut walls.
Toxicity and Contraindications in Piperazine
 Secretion of excess of saliva.
 Vomiting and nausea are the common side-effects of which are noticed in patients who are
using Piperazine.
 Diarrhoea and loss of water.
 Shivering and instability (Johnstone, Reierson and Bixby, 2012).
 Severe attacks of seizures.
 Restlessness, anxiety and depression.
 Auditory and visual hallucinations
 CNS (Central Nervous System) depression (Bolles, Fujiwara and Furge, 2014).
CONCLUSION
The report focussed on the various aspects of anti-epileptic and anti-psychotic drugs such as
Carbamazepine and Piperazine respectively. Mechanism of action, different receptors and
contraindication were also explored in this study. The study was based on two different styles . One
was based on summary for general public and the other was based on summary for scientific

audience. The former study included actions and mechanism of Carbamazepine and Piperazine
while the latter study included receptor activation mechanism, Absorption, Distribution,
Metabolism and excretion of both the drugs.
It also explored detailed mechanism of action of anti-epileptic and anti-psychotic drugs on
brain. pharmacokinetic and pharmacological characters of the drugs were also focussed in the above
report. In the end, different toxicity and contractions of Carbamazepine and Piperazine were
discussed so that adverse drug interaction between other drugs is minimized.

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Online

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