Tiamenidine

Chemical compound

C02AC (WHO)

Pharmacokinetic dataElimination half-life2.3–5 hours^[1]Identifiers

IUPAC name

N-(2-chloro-4-methylthiophen-3-yl)-4,5-dihydro-1H-imidazol-2-amine

CAS Number

31428-61-2^N

PubChem CID

39974

ChemSpider

36548^Y

UNII

195V08O55G

KEGG

D06127^Y

ChEMBL

ChEMBL295409^Y

CompTox Dashboard (EPA)

DTXSID80185349

Chemical and physical dataFormulaC₈H₁₀ClN₃SMolar mass215.70 g·mol⁻¹3D model (JSmol)

Interactive image

SMILES

Clc2scc(c2N/C1=N/CCN1)C

InChI

InChI=1S/C8H10ClN3S/c1-5-4-13-7(9)6(5)12-8-10-2-3-11-8/h4H,2-3H2,1H3,(H2,10,11,12)^Y
Key:CVWILQHZFWRYPB-UHFFFAOYSA-N^Y

^NY (what is this?) (verify)

Tiamenidine (BAN, USAN, INN, also known as thiamenidine, Hoe 440) is an imidazoline compound that shares many of the pharmacological properties of clonidine. It is a centrally-acting α₂ adrenergic receptor agonist (IC₅₀ = 9.1 nM).^[2] It also acts as an α₁-adrenergic receptor agonist to a far lesser extent (IC₅₀ = 4.85 μM).^[2] In hypertensive volunteers, like clonidine, it significantly increased sinus node recovery time and lowered cardiac output.^[3] It was marketed (as tiamenidine hydrochloride) by Sanofi-Aventis^[4] under the brand name Sundralen^[5] for the management of essential hypertension.^[6]

Synthesis

Reaction of thiourea 1 with methyl iodide gives the corresponding S-methyl analogue (2), followed by heating with ethylenediamine, completes the synthesis of tiamenidine (3).

References

^ Eckert HG, Baudner S, Weimer KE, Wissmann H (1981). "Determination of tiamenidine in biological specimens by radioimmunoassay". Arzneimittel-Forschung. 31 (3): 419–24. PMID 7194666.
^ ^a ^b Timmermans PB, de Jonge A, Thoolen MJ, Wilffert B, Batink H, van Zwieten PA (April 1984). "Quantitative relationships between alpha-adrenergic activity and binding affinity of alpha-adrenoceptor agonists and antagonists". Journal of Medicinal Chemistry. 27 (4): 495–503. doi:10.1021/jm00370a011. PMID 6142954.
^ Roden DM, Nadeau JH, Primm RK (June 1988). "Electrophysiologic and hemodynamic effects of chronic oral therapy with the alpha 2-agonists clonidine and tiamenidine in hypertensive volunteers". Clinical Pharmacology and Therapeutics. 43 (6): 648–54. doi:10.1038/clpt.1988.90. PMID 2897889. S2CID 44263714.
^ "Pharmaceutical and healthcare online databases. Tiamenidine Hydrochloride". Drugs-About.com. Retrieved 30 November 2015.
^ Ganten D, Mulrow PJ, eds. (2013). Pharmacology of Antihypertensive Therapeutics (1st ed.). [S.l.]: Springer-Verlag Berlin Heidelberg. p. 880. ISBN 978-3-642-74211-8.
^ Zamboulis C, Hossmann V, Dollery CT, Eckert H (October 1979). "Tiamenidine, a centrally acting antihypertensive drug in essential hypertension [proceedings]". British Journal of Clinical Pharmacology. 8 (4): 390P. doi:10.1111/j.1365-2125.1979.tb04737.x. PMID 508528.
^ US 3758476, 0 Rippel H, Ruschig H, Linder E, Schorr M, issued 1973

Sympatholytic (and closely related) antihypertensives (C02)

Sympatholytics
(antagonize α-adrenergic
vasoconstriction)

Central

α₂-Adrenergic receptor agonists	Clonidine Guanabenz Guanfacine Guanoxabenz Methyldopa^# Tiamenidine^‡
Adrenergic release inhibitors	Bethanidine Bretylium Debrisoquine Guanadrel Guanazodine Guancydine Guanethidine Guanoclor Guanoxan
Imidazoline receptor agonists	Moxonidine Rilmenidine Tolonidine
Ganglion-blocking/nicotinic antagonists	Hexamethonium^‡ Mecamylamine Pentolinium Trimethaphan

Peripheral

Indirect

Monoamine oxidase inhibitors	Pargyline^‡
VMAT inhibitors	Bietaserpine Deserpidine Methoserpidine Reserpine Syrosingopine
Tyrosine hydroxylase inhibitors	Metirosine

Direct

α₁-Adrenergic receptor blockers	Doxazosin Ketanserin Indoramin Prazosin Trimazosin Urapidil
Non-selective α-adrenergic receptor blockers	Phentolamine

Other antagonists

Serotonin receptor antagonists	Ketanserin Lidanserin
Endothelin receptor antagonists (for PHTooltip Pulmonary hypertension)	dual (Aprocitentan, Bosentan, Macitentan (+tadalafil)) selective (Ambrisentan, Sitaxentan)