Dr. Jibachha Sah,M.V.Sc( Veterinary pharmacology, TU,Nepal),posted lecturer notes on AUTONOMIC AND SYSTEMIC PHARMACOLOGY for B.V.Sc & A.H. 6 th semester veterinary students of College of veterinary science,Nepal Polytechnique Institute, Bharatpur, Bhojard, Chitwan, Nepal.I hope this lecture notes may be beneficial for other Nepalese veterinary students. Please send your comment and suggestion .Email:jibachhashah@gmail.com,moble,00977-9845024121

1. SEROTONIN or 5-hydroxy-
tryptamine and its antagonists
Dr. Jibachha Sah
M.V.Sc(Veterinary Pharmacology)
College of veterinary Science, NPI,
Bhojard,Chitwan

2. Serotonin:
A compound present in blood platelets and serum, which
constricts the blood vessels and acts as a neurotransmitter.
It is believed to help regulate mood and social behavior, appetite
and digestion, sleep, memory, and sexual desire and function.
Location
Enterochromaffin cell.

3. Enterochromaffin cell.
They are a type of enteroendocrine and neuroendocrine cell. They
reside alongside the epithelium lining the lumen of the digestive
tract and play a crucial role in gastrointestinal regulation,
particularly intestinal motility and secretion.

4. • Approximately 90% of the human and animal body's total
serotonin is located in the enterochromaffin cells in the alimentary
canal (gut), used to regulate intestinal movements.
• The remainder is synthesized in serotonergic neurons of the CNS,
where it has various functions including the regulation of mood,
appetite, and sleep.
• Serotonin secreted from the enterochromaffin cells eventually
finds its way out of tissues into the blood

5. IMPORTANCE OF SEROTONIIN
Serotonin is believed to play a central role in:
• Modulation of vasoconstriction
• Anger
• Aggression
• Body temperature
• Mood
• Sleep
• Sexual desire
• appetite
• Stimulation of vomiting reflex
• Memory and Learning

6. SOURCES
• Found abundantly in the gut and blood plasma, but it
can not enter the brain.
• Meat and Banana are the direct sources of serotonin.
• Main source: L-tryptophan, an amino acid, which is
found in proteins. So proteins are the main sources of serotonin:
Meat, eggs, milk, fishes Pulses
• Enough calcium, magnesium and oxygen are also needed
for serotonin production.
• Vitamin B6 also promotes its production.

7. Serotonin SYNTHESIS
Serotonin (5-hydroxytryptamine) is a small molecule that functions
both as a neurotransmitter in the central nervous system and as a
hormone in the periphery.
Serotonin is synthesized through a multistep pathway in which L-
tryptophan is converted into L-5OH-tryptophan by an enzyme called
tryptophan hydroxylase (Tph).

9. The primary effect of serotonin involves the increase in peristaltic
contraction through its effects on both enteric nervous system (ENS)
neurons and smooth muscle. 5-HT also activates a neural secretory
response, whereby binding at 5-HT1P receptors on myenteric neurons
triggers a signalling cascade in the submucosal plexus.
This results in the release of acetylcholine to initiate secretion from
the gut mucosa via release of chloride ions.

10. Clinical significance
Irritable bowel syndrome
The most common symptoms of irritable bowel syndromes is chronic, occasional
large bowel diarrhea, including frequent passage of small amounts of feces and
mucus, and constipation (dyschezia). Abdominal pain, bloating, vomiting, and
nausea may also occur.

11. Carcinoid syndrome
Carcinoid syndrome is a rare condition characterized by an abnormal
increase in circulating biologically active hormones, largely serotonin,
with early symptoms involving diarrhea, abdominal cramping and
episodic flushing.
Excess circulating serotonin is usually manufactured by EC-cell-
originated carcinoid tumors in the small bowel or appendix.
Tumors are slow growing, but can metastasise to the liver if aggressive.
They can also be present at other sites, particularly the lung and
stomach

12. pathway of serotonin synthesis from tryptophan in the diagram below.
Tryptophan-serotonin synthesis pathway

13. The most popular antidepressant medications like Prozac and Zoloft are selective
serotonin
Prozac(Fluoxetine ) is selective serotonin reuptake inhibitor (SSRI). It works by blocking the
absorption of the neurotransmitter serotonin in the brain. Regulating the amount
of serotonin helps brain cells transmit messages to each other. This results in a better and
more stable mood.
Drug available for clinical use

14. Prozac MOA
Prozac delays the body’s reuptake of serotonin — a monoamine neurotransmitter
thought to stabilize mood and contribute to feelings of well-being and happiness —
resulting in serotonin persisting longer when it is released. In other words, it’s a
serotonin enhancer. This process can thereby help combat things that trouble dog,
like anxiety and depression.
1. It helps reduce aggression.
2. It helps alleviate fear and anxiety conditions, like separation anxiety or
thunderstorm phobia.
3. It stabilizes mood and reduces impulsivity.
4. It is effective for treating obsessive-compulsive behaviors (OCD).
5. It often shuts down urine-marking in the home.
Usage

15. Prozac side effects
Dodman, who has used Prozac on animals for more than 25 years,
says dogs could experience pruritus (itch), or you may see anxiety,
tremors, restlessness or panting if they are given too high a dose of
Prozac. In his experience, reduced appetite and lack of energy are
the most common side effects.

16. Drug Interactions
There are many potential or hypothetical drug interactions for fluoxetine in dogs
and cats although many of these are extrapolated from experience in humans.
The list of potential drug interactions includes; acepromazine, amitraz (including the
flea/tick collars and dips) buspirone, cyproheptadine, diazepam, alprazolam, diuretics,
insulin, isoniazid, Monoamine Oxidase Inhibitors (MAO, a antidepressed drug) (selegiline),
pentazocine, phenytoin, propanolol, metoprolol, tramadol, tricyclic antidepressants,
trazodone, and warfarin.
MAOIs elevate the levels of norepinephrine, serotonin, and dopamine by inhibiting an
enzyme called monoamine oxidase.

17. Overdose
Signs of overdose in dogs and cats are : lethargy, hyper salivation, agitation. Seizures may
occur in dogs that have received a massive overdose.
Fluoxetine is well-absorbed orally and signs of overdose may present in 30 to 60 minutes.
If an overdose is recognized promptly, emesis and gastric lavage should be attempted in the
conscious animal. Activated charcoal and cathartics may be used subsequently as
warranted by clinical signs. Diazepam should be used in animals that are seizuring.
Available in 10 mg, 15 mg, and 20 mg tablets; 10 mg, 20 mg, 40 mg, and 90
mg capsules; oral liquid
DOGS: 1.0-2.0 mg/kg q24h; CATS 0.5-1.5 mg/kg q24h.

18. Zoloft (sertraline) is an antidepressant belonging to a group of drugs called selective
serotonin reuptake inhibitors (SSRIs).
Use
Sertraline affects chemicals in the brain that may be unbalanced in people with depression,
panic, anxiety, or obsessive-compulsive symptoms.
In dog and cat :
Sertraline, commonly known as Zoloft®, is used to treat aggression, fearful behaviors, and
anxiety related behaviors in dogs and cats.
Do not take Zoloft within 14 days before or 14 days after taken an MAO inhibitor. A
dangerous drug interaction could occur. MAO inhibitors include isocarboxazid, linezolid,
phenelzine, rasagiline, selegiline, and tranylcypromine.
Precaution

19. Zoloft side effects
Give emergency medical help if have signs of an allergic reaction to Zoloft: skin rash or hives
(with or without fever or joint pain); difficulty breathing; swelling of your face, lips, tongue, or
throat.
Dose
•The usual dose for sertraline in dogs is 1.25 to 2.5 mg per pound (2.5 to 5.0
mg/kg) orally every 24 hours.
•The cat dose is 0.5 to 2.0 mg per pound (1.0 to 4.0 mg/kg) orally every 24
hours.

20. High level of serotonin:
• Obsessive-compulsive disorders(OCD) e.g. compulsive
hand-washing
• Pulmonary vasoconstriction causing an acute or chronic
pulmonary hypertension • Cardiac fibrosis
Low levels of Serotonin:
• Irritability, Irrational emotions, Sudden unexplained tears,
Sleep disturbances, Depression, Suicidal tendencies
• When we have enough Serotonin we have: Emotional
stability, Reduces aggression, Sleep cycle, Appetite control

21. How is serotonin produced?
Serotonin is made via a unique biochemical conversion process. It
begins with tryptophan, a building block to proteins. Cells that
make serotonin use tryptophan hydroxylase, a chemical reactor
which, when combined with tryptophan, forms 5-hydroxytryptamine,
otherwise known as serotonin.
How can increase serotonin levels?
Foods high in simple carbohydrates, such as pastas, potatoes, bread, pastries,
pretzels, and popcorn, typically increase insulin levels and allow more tryptophan
(the natural amino acid building block for serotonin) to enter the brain, where the
brain cells can convert it to serotonin.

22. What gland produces serotonin?
pineal gland
The precursor to melatonin is serotonin, a neurotransmitter that
itself is derived from the amino acid tryptophan. Within the pineal
gland, serotonin is acetylated and then methylated to
yield melatonin.
What causes low levels of serotonin?
Toxic substances like heavy metals, pesticides, drug use, and some
prescription drugs can cause permanent damage to the nerve cells that
make serotonin and other neurotransmitters. Hormone changes cause low
levels of serotonin and neurotransmitter imbalances. Lack of sunlight
contributes to low serotonin levels.

23. 5-HT RECEPTORS
• Receptors are divided into 7 types: 5-HT1 to 5-HT7
• 5-HT1 group consist of 5 receptor subtypes:
5-HT1A
5-HT1B
5-HT1D
5-HT1E
5-HT1F