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Morphine (INN), the principal active agent in opium, is a powerful opioid analgesic drug. Like other opiates, morphine acts directly on the central nervous system (CNS) to relieve pain, and at synapses of the arcuate nucleus, in particular. Side effects include impairment of mental performance, euphoria, drowsiness, lethargy, and blurred vision. It also decreases hunger, inhibits the cough reflex, and produces constipation. Morphine is usually highly addictive, and tolerance and physical and psychological dependence develop quickly. more...

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Patients on morphine often report insomnia and nightmares.

The word derives from Morpheus, the god of dreams in Greek mythology.

Medical use

Administration

Morphine may be given parenterally as subcutaneous, intravenous, or epidural injections. The military sometimes issues morphine loaded in an autoinjector. Morphine can also be administered through a slow-release transdermal patch.

Orally, it comes as an elixir, concentrated solution, powder (for compounding) or in tablet form. Morphine is rarely supplied in suppository form. Due to its poor oral bioavailability, oral morphine is only one-sixth to one-third of the potency of parenteral morphine. Morphine is available in extended-release capsules for chronic administration, as well as immediate-release formulations.

Uses

Morphine is used legally:

analgesic in hospital settings for
- Pain after surgery
- Pain associated with trauma
In the relief of moderate to severe chronic pain
- Cancer pain
- Tooth extraction
As an adjunct to general anesthesia
In epidural anesthesia
For palliative care (i.e. to alleviate pain without curing the underlying reason for it)
As an antitussive for severe cough
As an antidiarrheal in chronic conditions (e.g., for diarrhea associated with AIDS)

Contraindications

Acute pancreatitis (this may be a result of morphine use as well)
Renal failure (due to accumulation of the metabolite morphine-6-glucuronide)

Pharmacology

Morphine is an opioid agonist whose main effect is binding to the µ-receptors in the central nervous system. This is thought to be the reason behind the analgesia, euphoria, physical dependence and respiratory depression. Morphine also binds with k-receptors, which are thought to mediate spinal analgesia, miosis and sedation.

Legal classification

In the United Kingdom, morphine is listed as a Class A drug under the Misuse of Drugs Act 1971.

In the United States, morphine is classified as a Schedule II drug under the Controlled Substances Act.

Internationally, morphine is a Schedule I drug under the Single Convention on Narcotic Drugs.

History

Morphine was first isolated in 1804 by the German pharmacist Friedrich Wilhelm Adam Sertürner, who named it "morphium" after Morpheus, the Greek god of dreams. But it was not until the development of the hypodermic needle (1853) that its use spread. It was used for pain relief, and as a "cure" for opium and alcohol addiction. Its extensive use during the American Civil War resulted in over 400,000 sufferers from the "soldier's disease" (addiction), though some believe this to be erroneous .

Read more at Wikipedia.org

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Ligand and Cardinal Health Execute New Five-Year Agreement to Manufacture and Package AVINZA; Key Second Source of Supply for Ligand's Largest Product
From Business Wire, 3/3/04

Business Editors/Health/Medical Writers

BIOWIRE2K

SAN DIEGO--(BUSINESS WIRE)--March 3, 2004

Ligand Pharmaceuticals Incorporated (Nasdaq: LGND) announced today it has entered into an agreement with Cardinal Health PTS, LLC, a subsidiary of Cardinal Health Inc. (NYSE: CAH), for the manufacturing and packaging of AVINZA(R) (morphine sulfate extended-release capsules). Under a long-term contract, AVINZA will be manufactured at the Cardinal Health facility located in Winchester, Kentucky. Ligand and Cardinal Health have an existing relationship for the fill/finish of Targretin(R) capsules.

Under the terms of the new agreement, upon the successful completion of technology transfer and regulatory approval, manufacturing will commence for a five-year term. Ligand has an option to extend for an additional two-year period. During the interim, Ligand and Cardinal Health will work closely together in the qualification and validation of the facility. Ligand and Cardinal Health intend to file for regulatory approval in 2005. Financial terms of the contract were not disclosed.

"This new manufacturing and packaging agreement with Cardinal Health represents an important step toward realizing the full potential of AVINZA by providing for a near doubling of current production capacity as well as a second source of supply to meet the accelerating demand and sales of AVINZA," said Gian Aliprandi, senior vice president, technical supply and international operations. "We believe the addition of Cardinal Health as a second source, together with activities to expand current capacity, are necessary to fully support the long-term success of our co-promotion of AVINZA with Organon and its market potential. Cardinal Health has been a good manufacturing partner of Ligand, and we are pleased to expand our relationship to include AVINZA."

About AVINZA

In March 2002, the US Food and Drug Administration granted marketing approval for AVINZA for once-daily treatment of moderate to severe pain in patients who require continuous, around-the-clock opioid therapy for an extended period of time. AVINZA was developed by Elan, which licensed the US and Canadian rights to Ligand in 1998. Under its license and supply agreement with Elan, amended in 2002, Ligand retained the right to qualify and purchase AVINZA from a second manufacturing source.

About Ligand

Ligand discovers, develops and markets new drugs that address critical unmet medical needs of patients in the areas of cancer, pain, skin diseases, men's and women's hormone-related diseases, osteoporosis, metabolic disorders, and cardiovascular and inflammatory diseases. Ligand's proprietary drug discovery and development programs are based on its leadership position in gene transcription technology, primarily related to Intracellular Receptors (IRs) and Signal Transducers and Activators of Transcription (STATs). For more information, go to www.ligand.com.

Caution Regarding Forward-Looking Statements

This news release contains certain forward-looking statements by Ligand that involve risks and uncertainties and reflect the company's judgment as of the date of this release. These statements include co-promotion, technology transfer, market potential, demand and sales, commencement of manufacturing, and manufacturing capacity. Actual events or results may differ from Ligand's expectations. There can be no assurance that co-promotion will be successful, that AVINZA will reach its potential or expectations, that initiation of a second source will be successful, or that our suppliers will be able to deliver products adequately and reliably in the future. Additional information concerning these and other risk factors affecting Ligand's business can be found in prior press releases as well as in the company's public periodic filings with the Securities and Exchange Commission, which are available via www.ligand.com. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

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