Apomorphine
From DrugPedia: A Wikipedia for Drug discovery
| Apomorphine
| |
| Systematic (IUPAC) name | |
| N/A | |
| Identifiers | |
| CAS number | ? |
| ATC code | ? |
| PubChem | |
| Chemical data | |
| Formula | C34H38Cl2N2O5 |
| Mol. mass | 625.58192 |
| SMILES | & |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
? |
| Legal status | |
| Routes | ? |
Contents |
[edit] Description
A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use.
Apomorphine is a type of dopaminergic agonist (agonist of the D1 and D2 type dopamine receptors), historically a morphine decomposition product by boiling with concentrated acid, hence the name. It does not actually contain morphine or its skeleton, or bind to opioid receptors. Apomorphine is a relatively non-selective dopamine receptor agonist, having possible slightly higher affinity for D2-like dopamine receptors.
Historically, apomorphine has been tried for a variety of uses including psychiatric treatment of homosexuality in the early 20th century. Currently, apomorphine is used in the treatment of Parkinson's disease and (under the name Uprima) of erectile dysfunction. It was also successfully used in the treatment of heroin addiction, a purpose for which it was championed by the author William S. Burroughs. It is a potent emetic (i.e. it induces vomiting) and should not be administered without an antiemetic such as domperidone. The emetic properties of apomorphine are exploited in veterinary medicine to induce therapeutic emesis in canines that have recently ingested toxic or foreign substances.
For treatment of erectile dysfunction, it is believed that dopamine receptors in the hypothalamic region of the brain are the main target, as although dopamine receptors in the penis do facilitate erection, they do so far more weakly than those in the brain.
Apomorphine is colourless as a liquid but stains green. Therefore care must be taken to avoid splashes. Apormophine does not remain stable for more than 24 hours in a plastic container, so syringes are discarded if not used within 24 hours.
[edit] Use in Parkinson's disease
First mooted as a treatment for Parkinson's disease as early as 1951, its clinical use was first reported in 1970 by Cotzias et al, although its emetic properties and short half-life made oral use impractical. A later study found that combining the drug with the antiemetic domperidone improved results significantly.
Therapeutic use in Parkinson's disease is effective because of the drug's strong dopaminergic action, with a rapid effect (within 3-20 minutes of injection) but a brief duration. While apomorphine can be used in combination with l-dopa, the intention is usually to wean patients off of this, as by this stage they will probably be experiencing a great deal of dopa-induced dyskinesias and "off" periods. Following a successful apomorphine challenge, training of patient and caregiver, and careful dose titration, there is no reason why an apomorphine pump can not be an effective monotherapy.
[edit] Erectile dysfunction
Apomorphine hydrochloride (trade name "Uprima") is used in the treatment of erectile dysfunction (male impotence). It is its mode of stimulating dopamine in the brain which is believed to enhance the sexual response. It was found to be of poor efficacy in a large-scale study by Researchers at the UK's Drug Safety Research Unit and University of Portsmouth and discontinued in the UK in January 2006. Around 65-70% of doctors felt it was ineffective, with 60% of over 11,000 patients (avg age 61) discontinuing in month 1 and a further 23% in month 2.
[edit] Alzheimer's disease
Apomorphine has been reported to be an inhibitor of Beta amyloid fibril formation, and may thus have potential as a therapeutic for Alzheimer's disease.
[edit] General Properties
*Molecular Weight
625.58192
*Molecular Formula
C34H38Cl2N2O5
*IUPAC NAME
N/A
*Canonical Smiles
CN1CCC2=CC=CC3=C2C1CC4=C3C(=C(C=C4)O)O.CN1CCC2=CC=CC3=C2C1CC4=C3C(=C(C=C4)O)O.O.Cl.Cl
*Isomeric Smiles
CN1CCC2=CC=CC3=C2[C@H]1CC4=C3C(=C(C=C4)O)O.CN1CCC2=CC=CC3=C2[C@H]1CC4=C3C(=C(C=C4)O)O.O.Cl.Cl
*XLogP
N/A
*Topological Polar Surface Area
88.4
