{{Short description|Antihypertensive drug}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Drugbox | IUPAC_name = 6-({3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl}amino)-1,3-dimethylpyrimidine-2,4(1''H'',3''H'')-dione | image = Urapidil structure.svg | image_class = skin-invert-image | width = 250px
<!--Clinical data--> | tradename = | Drugs.com = {{drugs.com|international|urapidil}} | pregnancy_category = | legal_status = Rx-only | routes_of_administration = Oral
<!--Pharmacokinetic data--> | bioavailability = | metabolism = | elimination_half-life = | excretion =
<!--Identifiers--> | CAS_number = 34661-75-1 | CAS_supplemental = <br />64887-14-5 (HCl) | ATC_prefix = C02 | ATC_suffix = CA06 | PubChem = 5639 | DrugBank = DB12661 | ChemSpiderID = 5437 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = A78GF17HJS | KEGG = D01333 | ChEMBL = 279229
<!--Chemical data--> | C=20 | H=29 | N=5 | O=3 | smiles = O=C1\C=C(/N(C(=O)N1C)C)NCCCN3CCN(c2ccccc2OC)CC3 | StdInChI = 1S/C20H29N5O3/c1-22-18(15-19(26)23(2)20(22)27)21-9-6-10-24-11-13-25(14-12-24)16-7-4-5-8-17(16)28-3/h4-5,7-8,15,21H,6,9-14H2,1-3H3 | StdInChIKey = ICMGLRUYEQNHPF-UHFFFAOYSA-N }}
'''Urapidil''' is a sympatholytic antihypertensive drug. It acts as an α<sub>1</sub>-adrenoceptor antagonist and as an 5-HT<sub>1A</sub> receptor agonist.<ref name="pmid1855130">{{cite journal | vauthors = Ramage AG | title = The mechanism of the sympathoinhibitory action of urapidil: role of 5-HT1A receptors | journal = British Journal of Pharmacology | volume = 102 | issue = 4 | pages = 998–1002 | date = April 1991 | pmid = 1855130 | pmc = 1917978 | doi = 10.1111/j.1476-5381.1991.tb12290.x }}</ref> Although an initial report suggested that urapidil was also an α<sub>2</sub>-adrenoceptor agonist,<ref name="pmid228944">{{cite journal | vauthors = Eltze M | title = Investigations on the mode of action of a new antihypertensive drug, urapidil, in the isolated rat vas deferens | journal = European Journal of Pharmacology | volume = 59 | issue = 1–2 | pages = 1–9 | date = October 1979 | pmid = 228944 | doi = 10.1016/0014-2999(79)90018-9 }}</ref> this was not substantiated in later studies that demonstrated it was devoid of agonist actions in the dog saphenous vein and the guinea-pig ileum.<ref name="pmid6097380">{{cite journal | vauthors = Verberne AJ, Rand MJ | title = Pharmacological activities of the antihypertensive drug urapidil in the rat | journal = Clinical and Experimental Pharmacology & Physiology | volume = 11 | issue = 4 | pages = 407–411 | year = 1984 | pmid = 6097380 | doi = 10.1111/j.1440-1681.1984.tb00289.x | s2cid = 22522953 }}</ref> Unlike some other α<sub>1</sub>-adrenoceptor antagonists, urapidil does not elicit reflex tachycardia, and this may be related to its weak β<sub>1</sub>-adrenoceptor antagonist activity,<ref>{{cite book |vauthors=Schoetensack W, Bruckschen EG, Zech K | chapter = Urapidil |pages=19 |year=1983 | title = New Drugs Annual: Cardiovascular Drugs}}</ref><ref name="pmid2984023">{{cite journal | vauthors = Verberne AJ, Rand MJ | title = Effect of urapidil on beta-adrenoceptors of rat atria | journal = European Journal of Pharmacology | volume = 108 | issue = 2 | pages = 193–196 | date = January 1985 | pmid = 2984023 | doi = 10.1016/0014-2999(85)90725-3 }}</ref> as well as its effect on cardiac vagal drive.<ref name="pmid1702490">{{cite journal | vauthors = Ramage AG | title = Influence of 5-HT1A receptor agonists on sympathetic and parasympathetic nerve activity | journal = Journal of Cardiovascular Pharmacology | volume = 15 | issue = Suppl 7 | pages = S75–S85 | year = 1990 | pmid = 1702490 | doi = 10.1097/00005344-199001001-00010 | doi-access = free }}</ref> Urapidil is currently not approved by the U.S. Food and Drug Administration, but it is available in Europe.
== Medical uses ==
=== D/T and reperfusion injuries === Urapidil has been determined to aid in the recovery of torsion detorsion (T/D) injuries in ovaries and testes, as well as ischemia-reperfusion (I/R) renal injuries. Both of these conditions are directly associated with one another as T/D injuries commonly lead to ischemia, or the lack of blood flow.<ref name="Erdoğan_2022">{{Cite journal | vauthors = Erdoğan DG, Tanyeli A, Güler MC, Eraslan E, Çomaklı S, Doğanay S |date=2022 |title=Beneficial Effects of Urapidil against Renal Ischemia Reperfusion-Related Renal Injury |url=https://scie.online/jvi.aspx?un=SCIE-89421&volume= |journal=Southern Clinics of Istanbul Eurasia |volume=33 |issue=2 |pages=198–202 |doi=10.14744/scie.2022.89421|doi-access=free }}</ref><ref name="Güler_2021">{{cite journal | vauthors = Güler MC, Tanyeli A, Erdoğan DG, Eraslan E, Çomaklı S, Polat E, Doğanay S | title = Urapidil alleviates ovarian torsion detorsion injury via regulating oxidative stress, apoptosis, autophagia, and inflammation | journal = Iranian Journal of Basic Medical Sciences | volume = 24 | issue = 7 | pages = 935–942 | date = July 2021 | pmid = 34712424 | pmc = 8528257 | doi = 10.22038/ijbms.2021.57196.12736 }}</ref><ref name="Meštrović_2017">{{cite journal | vauthors = Meštrović J, Pogorelić Z, Drmić-Hofman I, Vilović K, Todorić D, Popović M | title = Protective effect of urapidil on testicular torsion-detorsion injury in rats | journal = Surgery Today | volume = 47 | issue = 3 | pages = 393–398 | date = March 2017 | pmid = 27444029 | doi = 10.1007/s00595-016-1388-3 }}</ref> Urapidil is able to reduce inflammatory response, apoptosis and act as an antioxidant through a variety of pathways.<ref name="Güler_2021" /> During the detorsion phase of an injury, reperfusion, or the restoration of blood flow is important, but can also cause injuries to the affected tissue through apoptosis and the generation of ROS.<ref name="Güler_2021" /><ref name="Erdoğan_2022" /> Oxidative stress also plays a vital role in D/T and I/R injuries and is marked by malondialdehyde, or MDA, levels.<ref name="Erdoğan_2022" /><ref name="Meštrović_2017" /> MDA can also contribute to tissue damage, particularly by encouraging polymerization and cross-linking of the membranes of the affected cells.<ref name="Güler_2021" /> Through various studies performed within the past decade, it has been found that urapidil can treat T/D and I/R injuries, particularly stemming from autophagy, apoptosis, and inflammation, by elevating levels of SOD, TAS, and GPx within the cell.<ref name="Güler_2021" /><ref name="Meštrović_2017" /> Both SOD and GPx help to counteract the negative effects of ROS which injures tissue through lipid peroxidation and by damaging DNA.<ref name="Güler_2021" /> Additionally, urapidil has the ability to counteract autophagy by lowering the quantity of autophagosome marker LC3B and caspase-3 which also plays a critical role in autophagy regulation.<ref name="Güler_2021" /> thumb|Urapidil mediciation for treatment
== See also == * Naftopidil
== References == {{Reflist}}
{{Antihypertensives}} {{Adrenergic receptor modulators}} {{Serotonin receptor modulators}} {{Piperazines}}
Category:5-HT1A agonists Category:Alpha-1 blockers Category:Beta blockers Category:Chemical substances for emergency medicine Category:Piperazines Category:Lactams Category:Pyrimidines Category:2-Methoxyphenyl compounds