Chemistry:Ciraparantag
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| Other names | PER977; N1,N1′-[Piperazine-1,4-diylbis(propane-1,3-diyl)]bis-L-argininamide |
| Routes of administration | Intravenous |
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| Pharmacokinetic data | |
| Onset of action | 10 min |
| Duration of action | 24 hours |
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| Formula | C22H48N12O2 |
| Molar mass | 512.708 g·mol−1 |
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Ciraparantag (aripazine) is a drug under investigation as an antidote for a number of anticoagulant (anti-blood clotting) drugs, including factor Xa inhibitors (rivaroxaban, apixaban and edoxaban), dabigatran, and heparins (including fondaparinux, low molecular weight heparins (LMWH), and unfractionated heparin).[1][2]
Medical uses
Ciraparantag significantly reverses anticoagulation induced by a therapeutic dose of edoxaban within 10 minutes following injection.[3] This return to normal haemostasis persists over 24 hours following a single intravenous dose of the drug.[4] In addition to edoxaban, it also reverses the actions of LMWH and dabigatran.[5]
Pharmacology
Mechanism of action
According to in vitro studies, the substance binds directly to anticoagulants via hydrogen bonds and charge-charge interactions [3] from or to various parts of the molecule:[1]
| Hydrogen bonds | Rivaroxaban | Apixaban | Edoxaban | Dabigatran | Heparins |
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| Guanidine part | 
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| α-Amino group |
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| Amide nitrogen |
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| Amide oxygen |
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Chemistry
Ciraparantag consists of two L-arginine units connected with a piperazine containing linker chain.[1]
See also
References
- ↑ 1.0 1.1 1.2 (in German) Neue Arzneimittel. Fall 2015.
- ↑ "Universal, class-specific and drug-specific reversal agents for the new oral anticoagulants". Journal of Thrombosis and Thrombolysis 41 (2): 248–52. February 2016. doi:10.1007/s11239-015-1288-1. PMID 26449414.
- ↑ 3.0 3.1 "Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban". Thrombosis and Haemostasis 117 (2): 238–245. January 2017. doi:10.1160/TH16-03-0224. PMID 27853809.
- ↑ "Antidote for new oral anticoagulants: mechanism of action and binding specificity of PER977.". J Thromb Haemost 11 (suppl 2): 1–84. June 2013. http://www.eventure-online.com/eventure/publicAbstractView.do?id=226718&congressId=6839andhttp://www.perosphere.com/content/presentations/documents/Perosphere_ISTH_Talk.
- ↑ "PER977 reverses low molecular weight heparin in addition to IIa and Xa new oral anticoagulants". Journal of the American College of Cardiology 65 (10): A2056. March 2015. doi:10.1016/S0735-1097(15)62056-3.
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