Ibopamine

Ibopamine
Clinical data
AHFS/Drugs.com	International Drug Names
ATC code	C01CA16 (WHO) S01FB03 (WHO);
Identifiers
	IUPAC name 5-[2-(methylamino)ethyl]-2-[(2-methylpropanoyl)oxy]phenyl 2-methylpropanoate;
CAS Number	66195-31-1 ;
PubChem CID	68555;
ChemSpider	61829 ;
UNII	8ZCA2I2L11;
KEGG	D04488 ;
CompTox Dashboard (EPA)	DTXSID3023138 ;
ECHA InfoCard	100.060.189
Chemical and physical data
Formula	C17H25NO4
Molar mass	307.390 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(Oc1cc(ccc1OC(=O)C(C)C)CCNC)C(C)C;
	InChI InChI=1S/C17H25NO4/c1-11(2)16(19)21-14-7-6-13(8-9-18-5)10-15(14)22-17(20)12(3)4/h6-7,10-12,18H,8-9H2,1-5H3 ; Key:WDKXLLJDNUBYCY-UHFFFAOYSA-N ;
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Ibopamine is a sympathomimetic drug, designed as a prodrug of epinine (deoxyepinephrine or N-methyldopamine), used in ophthalmology.^[1] It induces mydriasis.^[2] It also has been investigated for use in the treatment of congestive heart failure.^[3]

It acts on D₁^[4]^[5] and α-adrenergic receptors as an agonist.^[6]

Ibopamine was first prepared by Casagrande and co-workers.^[7]

Instilled at 2% concentration, ibopamine exhibits several functions at ocular level such as pre- and post-operative mydriatic activity, D1 dopaminergic activity, etc.^[6]

Pharmacokinetics

Due to the esterases existing in the aqueous humour and ocular tissues, ibopamine can be rapidly hydrolysed to epinine which is the active molecule responsible for the mydriatic effect.^[8] The epinine, an analogue of dopamine, can stimulate dopamine receptors and to a lesser degree adrenergic receptors.^[9] Thus it is believed that epinine is the pharmacologically active moiety. It has been shown that the half-life of ibopamine is short to about 2 minutes in the aqueous humour owing to the fast hydrolysis.^[10] So ibopamine can not be found in the aqueous humor after instillation.

Pharmacodynamics

After being hydrolysed to epinine, ibopamine is able to stimulate the alpha-adrenergic and D1 dopaminergic receptors, thereby exhibiting mydriatic effects.^[11] In some randomized clinical trials, the D1 dopaminergic activity of ibopamine led to an increased production of aqueous humour and intraocular pressure (IOP) in primary open-angle glaucoma (POAG) patients.^[12]

Toxicology

At systemic and local levels, ibopamine has been proved to be of low toxicity. It is well tolerated since no obvious changes to the haematological and behavioural parameters have been observed after administration.^{[citation needed]} Ibopamine eye drop at 2% concentration, containing 1 mg of the compound, did not show any significant systemic side-effects and tachyphylaxis phenomena whereas the oral dosage is higher than 400 mg per day.^[6]

Clinical Use

A fast and short-lasting mydriasis can be induced by ibopamine without systemic side-effects.

References

^ Magacho L, Costa ML, Dessimoni A, de Avila MP (2006). "Comparison between the 1% and 2% ibopamine provocative test in primary open-angle glaucoma patients: sensitivity, specificity and tolerability". Arquivos Brasileiros de Oftalmologia. 69 (5): 695–699. doi:10.1590/S0004-27492006000500015. PMID 17187138.
^ Marchini G, Babighian S, Tosi R, Perfetti S, Bonomi L (June 2001). "Effects of 2% ibopamine on pupil, refraction, anterior segment anatomy and intraocular pressure". Journal of Ocular Pharmacology and Therapeutics. 17 (3): 215–223. doi:10.1089/108076801750295254. PMID 11436942.
^ van Veldhuisen DJ, Man in 't Veld AJ, Dunselman PH, Lok DJ, Dohmen HJ, Poortermans JC, et al. (November 1993). "Double-blind placebo-controlled study of ibopamine and digoxin in patients with mild to moderate heart failure: results of the Dutch Ibopamine Multicenter Trial (DIMT)". Journal of the American College of Cardiology. 22 (6): 1564–1573. doi:10.1016/0735-1097(93)90579-P. PMID 7901256.
^ Metra M, Missale C, Spano PF, Cas LD (May 1995). "Dopaminergic drugs in congestive heart failure: hemodynamic and neuroendocrine responses to ibopamine, dopamine, and dihydroergotoxine". Journal of Cardiovascular Pharmacology. 25 (5): 732–740. doi:10.1097/00005344-199505000-00008. PMID 7630152. S2CID 37607224.
^ Lieverse AG, Girbes AR, Van Veldhuisen DJ, Smit AJ, Zijlstra JG, Meijer S, et al. (July 1995). "The effects of ibopamine on glomerular filtration rate and plasma norepinephrine remain preserved during prolonged treatment in patients with congestive heart failure". European Heart Journal. 16 (7): 937–942. doi:10.1093/oxfordjournals.eurheartj.a061028. PMID 7498209.
^ ^a ^b ^c Giuffre I (2007). "Ibopamine stimulates α-adrenergic receptors and D1 dopaminergic receptors in the eye". Current Drug Therapy. 2 (2): 127–132. doi:10.2174/157488507780619112.
^ Casagrande C, Santangelo F, Saini C, Doggi F, Gerli F, Cerri O (February 1986). "Synthesis and chemical properties of ibopamine and of related esters of N-substituted dopamines--synthesis of ibopamine metabolites". Arzneimittel-Forschung. 36 (2A): 291–303. PMID 3707640.
^ Soldati L, Gianesello V, Galbiati I, Gazzaniga A, Virno M (February 1993). "Ocular pharmacokinetics and pharmacodynamics in rabbits of ibopamine, a new mydriatic agent". Experimental Eye Research. 56 (2): 247–254. doi:10.1006/exer.1993.1032. PMID 8096462.
^ Rajfer SI, Rossen JD, Douglas FL, Goldberg LI, Karrison T (April 1986). "Effects of long-term therapy with oral ibopamine on resting hemodynamics and exercise capacity in patients with heart failure: relationship to the generation of N-methyldopamine and to plasma norepinephrine levels". Circulation. 73 (4): 740–748. doi:10.1161/01.CIR.73.4.740. PMID 3948372.
^ Ugahary LC, Ganteris E, Veckeneer M, Cohen AC, Jansen J, Mulder PG, van Meurs JC (March 2006). "Topical ibopamine in the treatment of chronic ocular hypotony attributable to vitreoretinal surgery, uveitis, or penetrating trauma". American Journal of Ophthalmology. 141 (3): 571–573. doi:10.1016/j.ajo.2005.09.034. PMID 16490513.
^ Soldati L, Gianesello V, Galbiati I, Gazzaniga A, Virno M (February 1993). "Ocular pharmacokinetics and pharmacodynamics in rabbits of ibopamine, a new mydriatic agent". Experimental Eye Research. 56 (2): 247–254. doi:10.1006/exer.1993.1032. PMID 8096462.
^ De Gregorio F, Pecori Giraldi J, Pannarale L, Saccucci S, Virno M (1996-01-01). "Ibopamine in glaucoma diagnostics: a new pharmacological provocative test". International Ophthalmology. 20 (1–3): 151–155. doi:10.1007/BF00212962. PMID 9112180. S2CID 24889922.