MEDICINAL CHEMISTRY-III

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MEDICINAL CHEMISTRY-III

• Lecture 6
• Sat. 26/ 5/ 1432H
• Prof. Dr. Wafaa Zaghary

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• Morphine and other opium alkaloid occur mostly in
  combination with meconic acid as meconate salt or
  occur as sulphate salt (SO4--)

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Metabolism of morphine

• Conjugation with glucouronic acid.
• N-demethylation giving less active compound.

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Thebaine

• Chemical name ..
• The stimulant action of opium.
• The unsaturation in the alicyclic ring..
• The opium alkaloid thebaine, although
  therapeutically it is important as the chemical
  starting point for commercial synthesis of some
  opiate.

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• Thebaine is used as precursor for preparation of
  morphine and its derivatives as follow
• A. Preparation of Morphine

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B. Preparation of Oxomorphone, Oxocodone,
Naloxone Naltrexone
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Second Morphine Modifications in
1938
Pethidine ( Meperidine) It was the first fully
synthetic analgesic with morphine like
activity. It has lower and shorter duration of
action than morphine.
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Mepiridine Hydrochloride
- antispasmodic action due to papaverine-like
depression of smooth muscle - used as analgesic
especially where the pain is due to spastic
conditions of intestine, uterus, bladder,
bronchi, and kidney. - Possesses addiction
liability
Ethyl-1-methyl-4-phenyl-4-piperidine -carboxylate

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Second Morphine Modifications in
1938

• Methadone
• 6-dimethylamino-4,4-diphenylheptane-3-one
• Levomethadone is the active isomer which is
  similar to morpine in potency and side effects.
• It has oral availability and a long duration of
  action.
• replace morphine in withdrawal symptoms

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Fentanyl Citrate
- 50-time more active, rapid onset of action
(4), short duration. - S.E respiratory
depression and bradycardia - used as adjunct to
anesthesia in surgery.
N-(1-phenethyl-4-piperidinyl)-N-phenyl
propionamide
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Tramadol

• Cis-2-dimethylamiomethyl-1-(3-methoxy-
  phenyl)-cyclohexanol.
• It is a newer synthetic analgesic with weak mu
  agonist effects and some inhibitory action upon
  norepinephrine and serotonin uptake in CNS.
  (opioid non-opioid)