Slide 1: AMPHETAMINE
METABOLIC PATHWAY:
Deamination (followed by oxidation and reduction of the ketone formed)
N-oxidation
N-dealkylation
Hydroxylation of the aromatic ring
Hydroxylation of the β-carbon atom
Conjugation with glucuronic acid of the phenol and alcohol
products from the ketone formed by deamination
Slide 2: BARBITURATES
METABOLIC PATHWAY:
Oxidation and complete removal of substituents at carbon 5
N-dealkylation of at N1 and N3
Desulfuration at carbon 2 (Thiobarbiturates)
Scission of the barbiturate ring at the 1:6 bond to give substituted
malonylureas
Slide 3: PHENOTHIAZINES
METABOLIC PATHWAY:
N-dealkylation in the N10 side chain
N-oxidation in the N10 side chain
Oxidation of the heterocyclic S atom to sulfoxide or sulfone
Hydroxylation of one or both aromatic rings
Conjugation of phenolic metabolites with glucuronic acid or sulfate
Scission of the N10 side chain
Slide 4: SULPHONAMIDE
METABOLIC PATHWAY:
Activation at the N4 amino group
Conjugation with glucuronic acid sulfate at the N4 amino group
Acetylation or conjugation with glucuronic acid at the N1 amino group
Hydroxylation and conjugation in the heterocyclic ring, R
Slide 5: PHENYTOIN
METABOLIC PATHWAY:
Hydroxylation of one aromatic ring
Conjugation of phenolic products with glucuronic acid or sulfate
Hydrolytic scission of the hydantoin ring at the bond between
carbons 3 and 4 to give 5,5-diphenylhydantoic acid
Slide 6: MEPERIDINE
METABOLIC PATHWAY:
Hydrolysis of ester to acid
N-dealkylation
Hydroxylation of aromatic ring
N-oxidation
Both N-dealkylation and hydrolysis
Conjugation of phenolic products
Slide 7: PENTAZOCINE
METABOLIC PATHWAY:
Hydroxylation of terminal methyl groups of the alkenyl side chain
to give cis and trans (major) alcohols
Oxidation of hydroxymethyl product of the alkenyl side chain to
carboxylic acids
Reduction of alkenyl side chain and oxidation of terminal methyl
group
Slide 8: COCAINE
METABOLIC PATHWAY:
Hydrolysis of methyl ester
Hydrolysis of benzoate ester
N-dealkylation
Both hydrolysis and N-dealkylation
Slide 9: PHENMETRAZINE
METABOLIC PATHWAY:
Oxidation to lactam
Aromatic hydroxylation
N-oxidation
Conjugation of phenolic products
Slide 10: EPHEDRINE
METABOLIC PATHWAY:
N-dealkylation
Oxidative deamination
Oxidation of deaminated product to benzoic acid
Reduction of deaminated product to 1,2-diol
Slide 11: PROPRANOLOL
METABOLIC PATHWAY:
Aromatic hydroxylation at C-4l
N-dealkylation
Oxidative deamination
Oxidation of deaminated product to naphthoxylactic acid
Conjugation with glucuronic acid
O-dealkylation
Slide 12: INDOMETHACIN
METABOLIC PATHWAY:
O-demethylation
N-deacylation of p-chlorobenzoyl group
Both O-dealkylation and N-deacylation
Cojugation of phenolic products with glucuronic acid
Other conjugation products
Slide 13: PHENOXYLATE
METABOLIC PATHWAY:
Hydrolysis of ester to acid
Hydroxylation of one aromatic ring attached to the N-alkyl side chain
Slide 14: DIAZEPAM
METABOLIC PATHWAY:
N-dealkylation at N1
Hydroxylation at carbon 3
Conjugation of phenolic products with glucuronic acid
Both N-dealkylation of N1 and hydroxylation at carbon 3
Slide 15: PROSTAGLANDINS
METABOLIC PATHWAY:
Reduction of double bonds at carbons 5 and 6, and 13 and 14
Oxidation of 15-hydroxyl to ketone
β-oxidation of carbons 1,2,3 and 4
ω-oxidation of carbons 20 to acid
Slide 16: CYPROHEPTADINE
METABOLIC PATHWAY:
N-dealkylation
10,11-epoxide formation
Both N-dealkylation and 10,11-epoxidation
Slide 17: HYDRALAZINE
METABOLIC PATHWAY:
N-acetylation with cyclization to a methyl-s-triazolophthalazine
N-formylation with cyclization to an s-triazolophthalazine
Aromatic hydroxylation of benzene ring
Oxidative loss of hydrazinyl group to 1-hydroxy
Hydroxylation of methyl of methyl-s- triazolophthalazine
Conjugation with glucuronic acid
Slide 18: METHADONE
METABOLIC PATHWAY:
Reduction of ketone to hydroxyl
Aromatic hydroxylation of one aromatic ring
N-dealkylation of alcohol product
N-dealkylation with cyclization to pyrrolidine
Slide 19: LIDOCAINE
METABOLIC PATHWAY:
N-dealkylation
Oxidative cyclization to a 4-imidazolidone
N-oxidation of amide N
Aromatic hydroxylation ortho to methyl
Hydrolysis of amide
Slide 20: IMIPRAMINE
METABOLIC PATHWAY:
N-dealkylaion
Hydroxylation at C-11
Aromatic hydroxylation (C-2)
N-oxidation
Both N-dealkylation and hydroxylation
Slide 21: CIMETIDINE
METABOLIC PATHWAY:
S-oxidation
Hydroxylation of 5-methyl
Slide 22: VALPROIC ACID
METABOLIC PATHWAY:
CoA thioester
Dehydrogenation to (E) 2-ene
Dehydrogenation to (E) 2,4-diene
Dehydrogenation to 4-ene
3-Hydroxylation
Slide 23: PIROXICAM
METABOLIC PATHWAY:
Pyridine 3l-hydroxylation
Hydrolysis of amide
Decaboxylation
Slide 24: CAFFEINE
METABOLIC PATHWAY:
N3-demethylation
N1-demethylation
N7-demethylation to theophylline
C-8 oxidation to uric acids
Imidazole ring opened
Slide 25: THEOPHYLLINE
METABOLIC PATHWAY:
N3-demethylation
N1-demethylation
C-8 oxidation to uric acids
Imidazole ring opened
1-Me Xanthine to 1-Me uric acid-xanthine oxidase
Slide 26: NICOTINE
METABOLIC PATHWAY:
Pyrrolidine 5l-hydroxylation to continine
Pyrrolidine N-oxidation (FMO)
N-demethylation (Nornicotine and norcotinine)
Pyridine N-methylation
3l-Hydroxylation of cotinine
Slide 27: IBUPROFEN
METABOLIC PATHWAY:
CoA thioester and epimerization of R- to S+ enantiomer
Methyl hydroxylation to CH2OH
CH2OH to COOH
Acylglucuronide
Slide 28: TAMOXIFEN
METABOLIC PATHWAY:
N-demethylation
4l-hydroxylation
N-oxidation (FMO)
4-O-sulfate
4-O-glucuronide
Slide 29: LOVASTATIN
METABOLIC PATHWAY:
6l-hydroxylation
3l-side chain hydroxylation
3l-hydroxylation
β-oxidation of lactone
O-glucuronides
Slide 30: CIPROFLOXACIN
METABOLIC PATHWAY:
Piperazine 3l-hydroxylation
N-sulfation
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