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Name: Saumya S
Reg. no.: 15BBT0054
Date: 18/9/17
Assignment 1
INDIAN PHARMACOPEIA
BACLOFEN:
INTRODUCTION:
Baclofen is a gamma-amino-butyric acid (GABA) derivative used as a skeletal muscle
relaxant. Baclofen stimulates GABA-B receptors leading to decreased frequency and amplitude
of muscle spasms. It is especially useful in treating muscle spasticity associated with spinal cord
injury. It appears to act primarily at the spinal cord level by inhibiting spinal polysynaptic
afferent pathways and, to a lesser extent, monosynaptic afferent pathways.
Pharmacodynamics:
Baclofen is a muscle relaxant and antispastic. Baclofen is useful for the alleviation of signs
and symptoms of spasticity resulting from multiple sclerosis, particularly for the relief of flexor
spasms and concomitant pain, clonus, and muscular rigidity.
Targets: Gamma-aminobutyric acid type B receptor subunit 1 and subunit 2 -
Component of a heterodimeric G-protein coupled receptor for GABA, formed by
GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to
bind agonists, while GABBR2 mediates coupling to G proteins. Ligand binding causes a
conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins)
and modulates the activity of down-stream effectors, such as adenylate cyclase.
Fig 1: Spinal cord and muscle showing the action of muscle relaxants. Black lines ending in
arrow heads represent chemicals or actions that enhance the target of the lines. Blue lines ending
in squares represent chemicals or actions that inhibit the target of the line.
Mechanism of Action:
Baclofen is a direct agonist at GABAB receptors. The precise mechanism of action of
Baclofen is not fully known. It is capable of inhibiting both monosynaptic and polysynaptic
reflexes at the spinal level, possibly by hyperpolarization of afferent terminals, although actions
at supraspinal sites may also occur and contribute to its clinical effect.
Fig 2: Mechanism of Action of Baclofen.
Absorption:
Rapidly and almost completely absorbed from the GI tract.
Metabolism:
~ 15% of the dose is metabolized in the liver, primarily by deamination. 70-80% of the
dose is excreted unchanged or as metabolites in urine and the remainder is excreted in feces.
Half-life:
2.5-4 hours
Route of elimination:
In a study using radiolabeled baclofen, approximately 85% of the dose was excreted
unchanged in the urine and feces. Baclofen is excreted primarily by the kidney as unchanged
drug; 70 - 80% of a dose appears in the urine as unchanged drug. The remainder is excreted as
unchanged drug in the feces or as metabolites in the urine and feces.
IDENTIFICATION:
A. Determine by infrared absorption spectrophotometry: Compare the spectrum with
that obtained with baclofen RS. When examined in the range 220 nm to 320 nm, a 0.07
per cent w/v solution shows three absorption maxima, at 259 nm, 266 nm and 275 nm.
The specific absorbance at these maxima are 9.8 to 10.8, 11.5 to 12.7 and 8.4 to 9.3,
respectively.
TESTS:
TYPES:
Identification:-
Identification:-
REFERENCES:
1. Indian Pharmacopeia
2. https://www.drugbank.ca/drugs/DB00181
3. http://www.uniprot.org/uniprot/Q9UBS5
4. https://www.ncbi.nlm.nih.gov/pubmed/1621492