Veterinary Neuropharmacology

PHARMACOLOGICAL ACTIONS

Receptors

• Based on the pharmacologic criteria, the receptors are classified as:
• Musculotropic (D type) and Neurotropic (M type).
• The recent classification involves numbering of the receptors like 5-HT₁, 5-HT₂, 5-HT₃ etc.

Pharmacological actions

• Multiple actions with great variations in species are noticed.
• Effects are more pronounced in smooth muscles and both central and peripheral nerves.
• It is a potent depolarizer of nerve endings and tachyphylaxis is very common.
• On cardiovascular system 
  • Arterioles are constricted by its action on the smooth muscles.
  • Arterioles also experience dilatation due to the release of EDRF.
  •  Serotonin also releases adrenaline from the adrenal medulla. Net reflexes are complex.
  • Due to a rapid intravenous injection, a triphasic curve represented by an early sharp fall in blood pressure, an early rise in blood pressure and a prolonged fall in blood pressure in recorded.
  • However, continuous slow infusion causes a prolonged fall in arterial pressure.
• On smooth muscles
  • Serotonin stimulates the gastrointestinal tract and increases the peristalsis causing diarrhoea.
  • Bronchial smooth muscles are also constricted, but it is less potent than histamine.
• On glands 
  • Serotonin inhibits gastric secretion of acid and pepsin and increases mucous production.
  • Hence serotonin is considered to have ulcer protective effect.
• On nerve endings of adrenal medulla 
  • Afferent nerve endings are activated. But, it is less potent in releasing catecholamines from the adrenal medulla.
• On respiration 
  • A brief stimulation of respiration with hyperventilation occurs.
• On platelets 
  • Serotonin causes a change in the shape of platelets and is a weak aggregator.
• On central nervous system 
  • Since serotonin crosses the blood brain barrier poorly, central nervous system effects are not much pronounced. Fluoxetine is used as an antidepressant because of its uptake inhibition of 5-HT in the CNS.

Pathophysiological role

• Neurotransmitter – Serotonin acts as a neurotransmitter in the brain. It is involved in sleep, temperature regulation, thought, cognitive function, behaviour and mood, vomiting and pain perception.
• As a precursor of metabolism serotonin helps in the maintenance of circadian rhythm.
• Neuroendocrine function – It controls the release of anterior pituitary hormones.
• Nausea and vomiting – Nausea and vomiting evoked by cytotoxic drugs and radiotherapy are mediated by serotonin.
• Migraine – Serotonin initiates the vasoconstrictor phase of migraine.
• Haemostasis – Platelets release 5HT during aggregation at the site of injury.
• Hypertension
• Intestinal motility