What is it?
Morphine is a potent opiate analgesic drug used to relieve severe pain, first isolated in 1804 by Friedrich Sertürner.
Morphine is the most abundant alkaloid found in opium (8 - 14% of its dry weight) and the first active principle purified from it.
Its IUPAC name is (5α,6α)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol, while its formula is C 17 H 19 NO 3.
In clinical medicine, morphine is regarded as a benchmark of opioid analgesics used to relieve severe pain or suffering, acting directly on the central nervous system(CNS). However morphine has a high potential for addiction, and tolerance and psychological dependence develop rapidly, although dependence can take several mouths to start.
Biosynthesis
The precursor of morphine is the reticuline, one of the alkaloids found in opium: during the biosynthesis, the main compounds obtained are salutaridine, thebaine, oripavine and codeine. Main enzymes are written on the picture.
More informations and details: Morphine Biosynthesis
Pharmacodynamic
It interacts predominantly with μ-opioid receptor, which are highly distributed in the human brain, more specifically in the hypothalamus, thalamus, nucleus caudatus, putamen, posterior amygdala and certain cortical areas (they can even be found on the terminal axons of primary afferents within the substantia gelatinosa of the spinal cord and in the spinal nucleus of the trigeminal nerve). After its binding (which is known to be very strong), morphine exerts its effect on the CNS and gastrointestinal tract, causing first analgesia and sedation. Activation of μ-receptors is also associated with euphoria/dysphoria, respiratory depression and physical dependence.
Morphine binds also κ-opioid and δ-opioid receptors: κ-opioid's action is associated with mitosis, psychomimetic effects and spinal analgesia, while δ-opioid is though to play a role in analgesia. Morphine does not bind σ-opioid receptor.
Opioid receptors
How it works?
Opioid receptors work like a G protein coupled receptor G i/o. After ligand binds its receptor, the pathway is both inhibitory and stimulatory: G protein inhibits adenylate cyclase and the opening of Ca2+ channel, so intracellular levels of cAMP and Ca2+ decrease, causing a less neurotransmitter release by the synapse. It stimulates instead the opening of rectifying K + channels resulting in membrane hyperpolarization and reduction of nervous activity and the activation of PLC and PKC.
Pharmacokinetic
Morphine is subject to extensive first-pass metabolism (it means that the concentration is greatly reduced before it reaches the systemic circulation). It's metabolized primarily in the liver, and more or less than 85% of a dose is excreted in the urine within 72 hours. First it's metabolized in morphine-3-glucuronide and morphine-6-glucuronide, because of UDP-glucuronosyl transferase-2B7. Morphine is also metabolized in brain and kidneys.
The elimination half-life of morphine is 120 minutes, with a slight differences between men and women.
Effects
Most important effect is respiratory depression, then the patient has miosis and vomiting, while he is obliviously sedated. It effects on the muscle of bowel and urinary tract, causing sphincter to contract and reducing the peristalsis, so the patient can suffer delayed emptying of the stomach, constipation, and may also lead to urinary retention.
Morphine is a CNS depressant, has a negative impact on anterograde and retrograde memory (but effects are minimal and transient) and motor abilities (no studies have shown a correlation between morphine and gross motor abilities).
However these effects are more pronounced in opioid-naive subjects than chronic users because morphine has minor effectiveness on chronic opioid users
Morphine side effects
