Mode of action

Zelmac: a novel approach to the treatment of IBS

Zelmac (tegaserod maleate) is the first serotonin type-4 (5-HT4) receptor agonist developed to target the GI tract: the first sensorimotor modulator

N

H

NH2

OH

Serotonin (5-HT)Tegaserod

O NHNH

NHN

NH

Zelmac: Tegaserod maleate

The first 5 Hydroxy tryptamine (5HT) partial agonist

Mimics the effect of serotonin in the gut

Highly selective on the 5 HT 4 subtype

is an aminoguanidine indole compound

Please view movie

Definitions

What is an agonist?

What is an antagonist?

Movie re-inforcement

Please view movie one for a full explanation of the agonist and antagonist

Please view movie 2 for to reinforce your understanding

Importance of serotonin (5-HT) in the GI tract

GI tract contains ~95% of the body’s 5-HT

Role of 5-HT in GI tract

–maintains normal physiology (peristalsis, sensitivity)

–pathophysiology (altered motor function, abdominalpain, vomiting)

Receptors: In the GI tract, 5-HT predominantly acts via 5-HT3 and 5-HT4 receptors

Grider J et al. Gastroenterology 1998;115:370–80

5-HT

Excitatorymotor neuron(concentration)

5-HT4 receptors

Inhibitorymotor neuron (relaxation)

Enterochromaffin cells

Interneurons

Sensoryneuron

Motor activity in IBS

Movie re-inforcement

Please view movie 3 for a detailed explanation of the action of serotonin in the gut.

Please view movie 4 for detailed explanation of the action of Zelmac