Apomorfin

Apomorfin
(IUPAC) ime
	(6aR)-6-metil-5,6,6a,7-tetrahidro-4H-dibenzo[de,g]hinolin-10,11-diol
Klinički podaci
Robne marke	Apokin
AHFS/Drugs.com	Monografija
MedlinePlus	a604020
Identifikatori
CAS broj	41372-20-7
ATC kod	G04BE07 N04BC07
PubChem	6005
DrugBank	DB00714
ChemSpider	5783
UNII	F39049Y068
KEGG	D07460
ChEBI	CHEBI:48538
ChEMBL	CHEMBL53
Hemijski podaci
Formula	C17H17NO2
Mol. masa	267,322 g/mol
SMILES	eMolekuli & PubHem
InChI
	InChI=1S/C17H17NO2/c1-18-8-7-10-3-2-4-12-15(10)13(18)9-11-5-6-14(19)17(20)16(11)12/h2-6,13,19-20H,7-9H2,1H3/t13-/m1/s1 ; Key: VMWNQDUVQKEIOC-CYBMUJFWSA-N
Farmakokinetički podaci
Bioraspoloživost	100% nakon supkutane injekcije
Vezivanje za proteine plazme	~50%
Metabolizam	Hepatički
Poluvreme eliminacije	40 minuta (opseg 30-60 minuta)
Farmakoinformacioni podaci
Trudnoća	?
Pravni status	℞ Prescription only
Način primene	Oralno, SC

Apomorfin (Apokin, Iksens, Spontan, Uprima) neselektivni dopaminski agonist koji aktivira D₁ slične i D₂ slične receptore, sa izvesnom preferencijom za D2 srodne podtipove.^[6] On je proizvod razlaganja morfina pri zagrevanju do ključanja sa koncentrovanom kiselinom, iz kog razloga njegovo ime sadrži sufiks morfin. Apomorfin ne sadrži morfinsku osnovu, niti se vezuje za opioidne receptore. Prefiks apo indicira da je ovo jedinjenje derivat aporfina.

Apomorfin je ispitan za moguću primenu na više indikacija, npr. lečenje impotencije.^[7] Apomorfin se koristi za tretiranje Parkinsonove bolesti. On je potentan emetik (i.e., on indukuje povraćanje) i potrebno je da se koristi zajedno sa antiemetikom poput domperidona. Emetička svojstava apomorfina su ispitana u veterini za indukovanje terapeutkog povraćanja kod pasa koji su progutali toksične ili neželjene supstance.

On je nezvanično uspešno korišten za tretiranje heroinske adikcije. Nedavna ispitivanja indiciraju da je apomorfin podesan marker za određivanje promena centralnog dopaminskog sistema uzrokovanih hroničnim konzumiranjem heroina.^[8] Klinički dokazi da je apomorfin efektivani i bezbedan za tretiranje opijatne adikcije nisu dostupni.^[9]

Farmakologija

Apomorfin poseduje afinitet za sledeće receptore:^[6]

D₁ (K_i = 372 nM)
D_2S (K_i = 35 nM)
D_2L (K_i = 83 nM)
D₃ (K_i = 26 nM)
D₄ (K_i = 4.4 nM)
D₅ (K_i = 15 nM)
5-HT_1A (K_i = 117 nM)
5-HT_2A (K_i = 120 nM)
5-HT_2B (K_i = 132 nM)
5-HT_2C (K_i = 102 nM)
α_1B-adrenergički (K_i = 676 nM)
α_1D-adrenergički (K_i = 65 nM)
α_2A-adrenergički (K_i = 141 nM)
α_2B-adrenergički (K_i = 66 nM)
α_2C-adrenergički (K_i = 36 nM)

Reference

↑ Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit
↑ Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.
↑ Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit
↑ Joanne Wixon, Douglas Kell (2000). „Website Review: The Kyoto Encyclopedia of Genes and Genomes — KEGG”. Yeast 17 (1): 48–55. DOI:10.1002/(SICI)1097-0061(200004)17:1<48::AID-YEA2>3.0.CO;2-H.
↑ Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit
↑ ^6,0 ^6,1 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. DOI:10.1124/jpet.102.039867. PMID 12388666.
↑ Matsumoto K, Yoshida M, Andersson K, Hedlund P (2005). „Effects in vitro and in vivo by apomorphine in the rat corpus cavernosum”. Br J Pharmacol 146 (2): 259–67. DOI:10.1038/sj.bjp.0706317. PMC 1576267. PMID 16025145.
↑ 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. DOI:10.1080/1355621021000006206. PMID 14578019.
↑ Dent JY (1949). “Apomorphine Treatment of Addiction.” British Journal of Addiction to Alcohol & Other Drugs 46 (1); 15-28. DOI: 10.1111/j.1360-0443.1949.tb04502.x

Povezano

Propilnorapomorfin

Vanjske veze

	Portal Medicina
	Portal Hemija

PDSP K_i baza podataka Arhivirano 2013-05-17 na Wayback Machine-u
„Apomorphine - Frequently Asked Questions”. Britannia Pharmaceuticals. Arhivirano iz originala na datum 2014-12-22. Pristupljeno 2022-05-01.
Andrew Lees and Kirsten Turner (2002). „Apomorphine for Parkinson's Disease” (PDF). Practical Neurology 2 (5): 280–287. DOI:10.1046/j.1474-7766.2002.00086.x. ^{[mrtav link]} - Detailed usage guide for Apomorphine pumps for Parkinson's

[1] Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit

[2] Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.

[3] Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit

[4] Joanne Wixon, Douglas Kell (2000). „Website Review: The Kyoto Encyclopedia of Genes and Genomes — KEGG”. Yeast 17 (1): 48–55. DOI:10.1002/(SICI)1097-0061(200004)17:1<48::AID-YEA2>3.0.CO;2-H.

[5] Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit

[pmid12388666-6] 6,0 ^6,1 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. DOI:10.1124/jpet.102.039867. PMID 12388666.

[7] Matsumoto K, Yoshida M, Andersson K, Hedlund P (2005). „Effects in vitro and in vivo by apomorphine in the rat corpus cavernosum”. Br J Pharmacol 146 (2): 259–67. DOI:10.1038/sj.bjp.0706317. PMC 1576267. PMID 16025145.

[8] 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. DOI:10.1080/1355621021000006206. PMID 14578019.

[9] Dent JY (1949). “Apomorphine Treatment of Addiction.” British Journal of Addiction to Alcohol & Other Drugs 46 (1); 15-28. DOI: 10.1111/j.1360-0443.1949.tb04502.x

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