Dihydroergotamine

IUPAC nomenclature

(2R,4R,7R)-N-[(1S,2S,4R,7S)-7-benzyl-2-hydroxy-4-methyl-5,8-dioxo-3-oxa-6,9-diazatricyclo[7.3.0.02,6]dodecan-4-yl]-6-methyl-6,11-diazatetracyclo[7.6.1.02,7.012,16]hexadeca-1(16),9,12,14-tetraene-4-carboxamide.

Classification

Dihydroergotamine is an ergot alkaloid.

Physiochemical Properties

Mechanism of Action

Dihydroergotamine is proposed to work on two theories:

1. Activation of 5-HT₁₀ receptors located on the intracranial blood vessels, which also includes the receptors on arterio-venous anastomoses. This results in vasoconstriction and thus, produces relief in migraine and headache.
2. Inhibition of pro-inflammatory neuropeptide release through activation of 5-HT₁₀ receptors on sensory nerve endings of the trigeminal system.

Structure Activity Relationship

• d-isomers of lysergic acid is inactive. It must be in the l-form.
• Antimigraine effect of the drug is due to the 9-10 double bond.

Method of synthesis

Dihydroergotamine can be synthesized from reduction (hydrogenation) of the double bond of the ergoline ring of ergotamine at the 9-0 position.

Therapeutic Uses

Dihydroergotamine is used for:

• Migraine headaches
• Cluster headaches
• Prevention of migrains

Side Effects

Side effects of Dihydroergotamine are:

• Increased sweating
• Diarrhea
• Vomiting
• Nausea
• Headache
• Drowsiness
• Dizziness

 MCQs

Q.1 Mechanism of action of dihydroergotamine depends on?

a) Activation of 5-HT₁₀ receptors located on the intracranial blood vessels

b) Inhibition of pro-inflammatory neuropeptide release through activation of 5-HT₁₀ receptors on sensory nerve endings of the trigeminal system

c) Both a) and b)

d) None of the above

Q.2 Therapeutic use of drug dihydroergotamine is/are?

a) Migraine headaches

b) Cluster headaches

c) Prevention of migrains

d) All of the above

Q.3 Which amongst the following are the correct statements with respect to the SAR of drug dihydrergotamine?

I. d-isomers of lysergic acid is inactive. It must be in the l-form.

II. Antimigraine effect of the drug is due to the 9-10 double bond.

a) I, II

b) I

c) II

d) NONE

Q.4 Dihydroergotamine can be synthesized from ergotamine by?

a) Halogination

b) Reduction

c) Halogination followed by reduction

d) None of the above

Q.5 Correct sequence for the True/False for the physiochemical properties of the drug Dihydroergotamine?

I. Molecular weight is 222.3 gm/mol.

II. Melting point is 219°C

III. it is having an imidazole ring

IV. Number of chiral carbon atoms is 3

a) TTFF

b) TFTF

c) FFTF

d) TTTT

Q.6 Trade name of Dihdroergotamine is?

a) D.H.E. 45

b) Alkeran

c) Mustine

d) Endoxan

 Q.7 Match the following drugs with their correct classifications-

a) i-A, ii-B, iii-C, iv-D

b) i-D, ii-B, iii-C, iv-A

c) i-C, ii-A, iii-B, iv-D

d) i-D, ii-B, iii-A, iv-C

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ANSWERS

1-c

2-d

3-a

4-b

5-a

6-a

7-a