Nalorphine

Opioid antagonist and analgesic

Nalorphine
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Nalorphine, also known as N-allylnormorphine, is a mixed opioid receptor agonist-antagonist. It was one of the first opioid antagonists to be discovered and has been used in the treatment of opioid overdose and in research settings to study opioid receptor activity.

Pharmacology

Nalorphine acts as an antagonist at the mu-opioid receptor and as a partial agonist at the kappa-opioid receptor. This dual action allows it to reverse the effects of opioid overdose, such as respiratory depression, while also producing some analgesic effects. However, its use is limited due to the dysphoric and psychotomimetic effects associated with kappa receptor activation.

History

Nalorphine was first synthesized in the 1950s as a derivative of morphine. It was initially used as a diagnostic tool to differentiate between opioid and non-opioid induced coma. Its ability to reverse opioid effects made it a valuable tool in emergency medicine before the development of more selective opioid antagonists like naloxone.

Synthesis

Nalorphine synthesis

The synthesis of nalorphine involves the modification of the morphine molecule. The key step is the introduction of a cyclopropylmethyl group at the nitrogen atom, which is achieved through a series of chemical reactions starting from morphine or its derivatives. This modification is crucial for its activity as an opioid antagonist.

Clinical Use

Nalorphine was used clinically to reverse the effects of opioid overdose, particularly in cases where respiratory depression was a concern. However, due to its side effects and the development of more effective and selective opioid antagonists, its use in clinical practice has declined.

Side Effects

The side effects of nalorphine are primarily related to its kappa-opioid receptor activity. These include dysphoria, hallucinations, and anxiety. These effects limit its use in clinical settings, especially when compared to other opioid antagonists that do not activate the kappa receptor.

Related Compounds

Nalorphine is structurally related to other opioid antagonists such as naloxone and naltrexone. These compounds share a similar mechanism of action but differ in their receptor selectivity and clinical applications.

Related pages

• Opioid receptor
• Naloxone
• Naltrexone
• Morphine