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Repositioning Candidate Details

Candidate ID: R0077
Source ID: DB00295
Source Type: approved; investigational
Compound Type: small molecule
Compound Name: Morphine
Synonyms:
Molecular Formula: C17H19NO3
SMILES: [H][C@@]12OC3=C(O)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])C=C[C@@H]2O
Structure:
DrugBank Description: Morphine is the main alkaloid of opium and it was first obtained from the poppy seeds in 1805.[A176035] It is the most potent analgesic for chronic pain but its use is limited due to the induction of tolerance, severe withdrawal symptoms and high risk of relapse and abuse.[A176050] In its pure form, morphine is ten times more potent than opium and due to this property, it was used extensively in the US Civil War which resulted in approximately 400,000 addicted soldiers. After this event, around the second half of the nineteenth-century, the science made several efforts to find a less addictive alternative which brought the synthesis of [heroin]. However, morphine is still the precursor to other opioids such as [codeine], [fentanyl], [methadone], [hydrocodone], [hydromorphone], [meperidine], and [oxycodone].[L5716] Morphine's first official product was developed by West-Ward Pharmaceuticals Int. and FDA approved in 1984.[L5713]
CAS Number: 57-27-2
Molecular Weight: 285.3377
DrugBank Indication: Morphine is used for the management of chronic moderate-to-severe pain.[A176050] Opioids, including morphine, can manage pain effectively when used for a short amount of time. The use of opioids for longer periods needs to be monitored as they can develop a physical dependence, addiction disorder and drug abuse.[L5728]
DrugBank Pharmacology: The binding of morphine in the opioid receptors blocks the transmission of nociceptive signals, it activates the signaling of pain-modulating neurons in the spinal cord and inhibits the transmission from primary afferent nociceptors to the dorsal horn sensory projection cells.[A176035] The onset of action is of 6-30 minutes.[A176035] The excess in the consumption of morphine and opioids, in general, can produce changes in the synaptic neuroplasticity mainly in the postsynaptic sites, dendritic terminals and modifications in the density.[A176056] Analysis of intravenous morphine showed that the attenuation of pain and analgesic effect was sex-dependent. The potency of the morphine effect is of around half in men when compared to the effect in women, as observed with an EC50 of 76 and 33 ng/ml respectively. As well, the effect of the active metabolite of morphine, morphine-6-glucuronide, was only about 22 times less potent than the morphine when analyzed in pupil constriction.[A176116]
DrugBank MoA: It is important to consider that about 85% of the effect observed by morphine administration is due to the activity of morphine-6-glucuronide.[A176059] Morphine and its metabolites act as agonists of the mu and the kappa opioid receptors which derive later into analgesia.[A176035] The mu-opioid receptor is a key part of the effect of morphine in the ventral tegmental area which reinforces the effects of morphine. However, in studies with delta opioid receptor knock-out mice, it was reported a reduction in the rewarding effect of morphine suggesting that the rewarding effect of morphine is related to activity towards the delta opioid receptor in the nucleus accumbens.[A176050] From the three target receptors of morphine, the mu receptor is associated with the side effects of the morphine such as modifications in the respiratory system and addiction.[A176056]
Targets: Mu-type opioid receptor; Kappa-type opioid receptor; Delta-type opioid receptor; Lymphocyte antigen 96
Inclusion Criteria: