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File:Apomorphine 3d.gif
Systematic (IUPAC) name
Clinical data
Trade names Apokyn
AHFS/Drugs.com monograph
MedlinePlus a604020
Pregnancy cat. B3 (AU) C (US)
Legal status Prescription Only (S4) (AU) -only (CA) POM (UK) -only (US)
Routes Oral, SC
Pharmacokinetic data
Bioavailability 100% following sc injection
Protein binding ~50%
Metabolism Hepatic
Half-life 40 minutes (range 30-60 minutes)
CAS number 58-00-4 7pxN
ATC code G04BE07 N04BC07
PubChem CID 6005
IUPHAR ligand 33
DrugBank DB00714
ChemSpider 5783 7pxY
UNII F39049Y068 7pxY
KEGG D07460 7pxY
ChEBI CHEBI:48538 7pxY
Chemical data
Formula C17H17NO2 
Mol. mass 267.322 g/mol
 14pxN (what is this?)  (verify)

Apomorphine (Apokyn, Ixense, Spontane, Uprima) is a non-selective dopamine agonist which activates both D1-like and D2-like receptors, with some preference for the latter subtypes.[1] It is historically a morphine decomposition product by boiling with concentrated acid, hence the -morphine suffix. Apomorphine does not actually contain morphine or its skeleton, nor does it bind to opioid receptors. The apo- prefix relates to it being an aporphine derivative.

Historically, apomorphine has been tried for a variety of uses including psychiatric treatment of homosexuality in the early 20th century, and more recently in treating erectile dysfunction. Currently, apomorphine is used in the treatment of Parkinson's disease. 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.

It was also successfully used as an unofficial treatment of heroin addiction, a purpose for which it was championed by the author William S. Burroughs. A recent study indicates that apomorphine might be a suitable marker for assessing central dopamine system alterations associated with chronic heroin consumption.[2] There is, however, no clinical evidence that apomorphine is an effective and safe treatment regimen for opiate addiction. Early studies involved aversion therapy in alcoholism and anxiety, and modern reports are rather anecdotal.[3]



Apomorphine was used with some notable success as a treatment for alcohol and morphine addiction. Its chief practitioner in the 1950s was Dr John Yerbury Dent 1888-1962 who, early on in his research, mistakenly believed that it was the emetic properties of apomorphine which were efficacious. Subsequently however he realised that it had deeper impact than mere aversion. It is now hypothesised that it is a neurobiological rebooter of the dopaminergic system and as such rewrites the "reward pathway"

Parkinson's disease

First mooted as a treatment for Parkinson's disease as early as 1951,[4] its clinical use was first reported in 1970 by Cotzias et al.,[5] 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.[6]

Therapeutic use in Parkinson's disease is effective because of the drug's strong dopaminergic action. When administered subcutaneously, apomorphine is the most effective dopamine agonist. Within 3–20 minutes of injection apomorphine demonstrates a magnitude of effect (ability to convert the patient with Parkinson's disease to the "on" state) that is comparable to l-dopa. A single subcutaneous injection lasts for up to 90 minutes.[7] While apomorphine can be used in combination with l-dopa, the intention is usually to reduce the l-dopa dosing, as by this stage the patient with Parkinson's disease will probably be experiencing a great deal of dopa-induced dyskinesias and "off" periods.[7] Following a successful apomorphine challenge, training of patient and caregiver, and careful dose titration, the patient can be maintained in the "on" state by the use of an apomorphine pump as an effective monotherapy.[7]

Erectile dysfunction

Apomorphine hydrochloride (trade name "Uprima", "Ixense") was a therapy 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[8] 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.[8] 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.[8][9] UK studies concentrated on males with generalized erectile dysfunction. Uprima affects desire and is not meant to produce a systemic effect unlike drugs such as Viagra, which affect circulation. In those males who have problems with desire as opposed to generalized erectile dysfunction, it works as expected.

Erections in men are generally classified into two categories: Reflexogenic erections, that is erections triggered by physical stimulus of the penis, and Psychogenic erections, which are triggered by sexual fantasies, thoughts and looking at things which are sexually stimulating. Psychogenic erections are generally gradually lost in men somewhere between the ages of 45 and 65. Apomorphine has been shown to restore Psychogenic erections in men who are otherwise unable to achieve them.

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.[10]

Opioid addiction

In his Deposition: Testimony Concerning a Sickness in the introduction to later editions of Naked Lunch, William S. Burroughs wrote that apomorphine treatment was the only effective cure to opioid addiction he has encountered. "The apomorphine cure is qualitatively different from other methods of cure. I have tried them all. Short reduction, slow reduction, cortisone, antihistamines, tranquilizers, sleeping cures, tolserol, reserpine. None of these cures lasted beyond the first opportunity to relapse. I can say that I was never metabolically cured until I took the apomorphine cure... The doctor, John Yerbury Dent, explained to me that apomorphine acts on the back brain to regulate the metabolism and normalize the blood stream in such a way that the enzyme stream of addiction is destroyed over a period of four to five days. Once the back brain is regulated apomorphine can be discontinued and only used in case of relapse. He goes on to lament the fact that as of his writing, little to no research has been done on apomorphine or variations of the drug to study its effects on curing addiction, and perhaps the possibility of retaining the positive effects while removing the side effect of vomiting. Despite his claims throughout his life, Burroughs never really cured his addiction and was back to using opiates within years of his apomorphine "cure". However, he insisted on apomorphine’s effectiveness in several works and interviews.


Apomorphine possesses affinity for the following receptors:[11]

It has > 1,000 nM affinity for 5-HT1B, 5-HT1D, and α1A-adrenergic, and > 10,000 nM affinity for β-adrenergic, H1, and mACh.[1]

Apomorphine behaves as a partial agonist at D2S (IA = 79%), D2L (IA= 53%), D3 (IA = 82%), and D4 (IA = 45%), and as an antagonist at 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, α1-adrenergic, and α2-adrenergic.[12][13] Though its efficacies at D1 and D5 are unclear, it is known to act as an agonist at these sites.[14]



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.


Apomorphine hydrochloride is synthesized by heating stoichiometric amounts of morphine and concentrated hydrochloric acid at 140 °C.[citation needed]

In popular culture

See also


  1. 1.0 1.1 Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A (November 2002). "Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes". The Journal of Pharmacology and Experimental Therapeutics 303 (2): 791–804. PMID 12388666. doi:10.1124/jpet.102.039867. 
  2. Guardia J, Casas M, Prat G, Trujols J, Segura L, Sánchez-Turet M (October 2002). "The apomorphine test: a biological marker for heroin dependence disorder?". Addict Biol 7 (4): 421–6. PMID 14578019. doi:10.1080/1355621021000006206. 
  3. Dent JY (1949). "Apomorphine Treatment of Addiction." British Journal of Addiction to Alcohol & Other Drugs 46 (1); 15-28. [1] doi:10.1111/j.1360-0443.1949.tb04502.x
  4. Schwab R, Amador L, Lettvin J (1951). "Apomorphine in Parkinson's disease". Trans Am Neurol Assoc 56: 251–3. PMID 14913646. 
  5. Cotzias G, Papavasiliou P, Fehling C, Kaufman B, Mena I (1970). "Similarities between neurologic effects of L-dopa and of apomorphine". N Engl J Med 282 (1): 31–3. PMID 4901383. doi:10.1056/NEJM197001012820107. 
  6. Corsini G, Del Zompo M, Gessa G, Mangoni A (1979). "Therapeutic efficacy of apomorphine combined with an extracerebral inhibitor of dopamine receptors in Parkinson's disease". Lancet 1 (8123): 954–6. PMID 87620. doi:10.1016/S0140-6736(79)91725-2. 
  7. 7.0 7.1 7.2 Chaudhuri K, Clough C (1998). "Subcutaneous apomorphine in Parkinson's disease: Effective yet underused". BMJ 316 (7132): 641. PMC 1112674. PMID 9522772. doi:10.1136/bmj.316.7132.641. 
  8. 8.0 8.1 8.2 Pharmaceutical Business Review, [ "Study shows Abbott's Uprima ineffective for most UK patients"]
  9. MedicineNet study review
  10. Lashuel HA, Hartley DM, Balakhaneh D, Aggarwal A, Teichberg S, Callaway DJE (2002). "New class of inhibitors of amyloid-beta fibril formation. Implications for the mechanism of pathogenesis in Alzheimer's disease". J Biol Chem 277 (45): 42881–42890. PMID 12167652. doi:10.1074/jbc.M206593200. 
  11. Roth, BL; Driscol, J (12 January 2011). "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 1 July 2014. 
  12. Newman-Tancredi A, Cussac D, Audinot V, et al. (November 2002). "Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. II. Agonist and antagonist properties at subtypes of dopamine D(2)-like receptor and alpha(1)/alpha(2)-adrenoceptor". The Journal of Pharmacology and Experimental Therapeutics 303 (2): 805–14. PMID 12388667. doi:10.1124/jpet.102.039875. 
  13. Newman-Tancredi A, Cussac D, Quentric Y, et al. (November 2002). "Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. III. Agonist and antagonist properties at serotonin, 5-HT(1) and 5-HT(2), receptor subtypes". The Journal of Pharmacology and Experimental Therapeutics 303 (2): 815–22. PMID 12388668. doi:10.1124/jpet.102.039883. 
  14. Hsieh GC, Hollingsworth PR, Martino B, et al. (January 2004). "Central mechanisms regulating penile erection in conscious rats: the dopaminergic systems related to the proerectile effect of apomorphine". The Journal of Pharmacology and Experimental Therapeutics 308 (1): 330–8. PMID 14569075. doi:10.1124/jpet.103.057455. 

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