References

pharmjournal

Разработка и регистрация лекарственных средств

Drug development & registration

2305-20662658-5049

LLC «CPHA»

pharmjournal-241

Research Article

РЕГУЛЯТОРНЫЕ ВОПРОСЫ

REGULATORY ISSUES

СИЛЬНОДЕЙСТВУЮЩИЕ НЕНАРКОТИЧЕСКИЕ АНАЛЬГЕТИКИ КАК НАПРАВЛЕНИЕ РАЗВИТИЯ ФАРМАЦЕВТИКИ

POTENT NON-NARCOTIC ANALGESICS AS А DIRECTION IN DEVELOPMENT OF PHARMACEUTICALS

Соснов

А. В.

Sosnov

A. V.

noemail@neicon.ru

Садовников

С. В.

Sadovnikov

S. V.

noemail@neicon.ru

Семченко

Ф. М.

Semchenko

F. M.

noemail@neicon.ru

Руфанов

К. А.

Rufanov

K. A.

noemail@neicon.ru

Тохмахчи

В. Н.

Tohmahchi

V. N.

noemail@neicon.ru

Соснова

А. А.

Sosnova

A. A.

noemail@neicon.ru

Тюрин

И. А.

Tyurin

I. A.

noemail@neicon.ru

ОАО ФНТЦ «Инверсия»Federal S&T Center «Inversiya»; The Federal State Unitary Enterprise State Pharmaceutical Plant (FSUE «GosZMP»)

ОАО ФНТЦ «Инверсия»Federal S&T Center «Inversiya»

ФГУП «Государственный завод медицинских препаратов» (ФГУП «ГосЗМП»)The Federal State Unitary Enterprise State Pharmaceutical Plant (FSUE «GosZMP»)

ГБУЗ «НИИ Скорой помощи им. Н.В. Склифосовского»N.V. Sklifosovsky Research Institute of Emergency Medicine

2016

09012019

01196206

2019

Соснов А.В., Садовников С.В., Семченко Ф.М., Руфанов К.А., Тохмахчи В.Н., Соснова А.А., Тюрин И.А.

Sosnov A.V., Sadovnikov S.V., Semchenko F.M., Rufanov K.A., Tohmahchi V.N., Sosnova A.A., Tyurin I.A.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.pharmjournal.ru/jour/article/view/241

В статье описаны подходы к выбору наиболее актуальных сильнодействующих ненаркотических анальгетиков среди веществ, находящихся на различных стадиях исследований и разработок. Препараты ненаркотических анальгетиков для купирования сильной и средней боли являются относительно новым направлением фармацевтики. Их внедрение в качестве альтернативы опиатам весьма актуально. Однако число реальных кандидатов крайне ограничено. В результате проведенного авторами анализа один из наиболее сильнодействующих ненаркотических анальгетиков - блокатор натриевых каналов нейронов ПНС тетродотоксин (ТТХ) был признан наиболее актуальным. В настоящее время ФГУП «ГосЗМП» проводит доклинические исследования инъекционного препарата на основе ТТХ.

The article describes some approaches to choice of the most potent non-narcotic analgesics among agents investigated in various R&D stages. Preparations non-narcotic analgesics for relief of severe and moderate pain are relatively new area of pharmaceuticals. Their application is very important as an alternative to opiates. However, the actual number of drug candidates is very limited. As a result of the authors analysis one of the most potent non-narcotic analgesics (PNS neurons sodium channel blocker) - Tetrodotoxin (TTX) was recognized as the most promising. Currently FSUE «GosZMP» conducting preclinical studies of injectable preparation of TTX.

болевой синдромсильнодействующий ненаркотический анальгетиксоединения-лидерыбиомишени нервной системыблокатор ионных каналовтетродотоксин

severe and moderate painpotent non-narcotic analgesiclead compoundsbiotargets of nervous systemion channel blockertetrodotoxin

References1

R.J. Gatchel, I.Z. Schultz. Handbook of Musculoskeletal Pain and Disability Disorders in the Workplace. - NY: Springer Science & Business Media, 2014. 509 р.

Report to the Ranking Member, Committee on Veterans’ Affairs, House of Representatives. DOD AND VA HEALTH CARE Medication Needs during Transitions May Not Be Managed for All Servicemembers. GAO-13-26. 2012.

E. Wax-Thibodeaux. New rules on narcotic painkillers cause grief for veterans and VA // The Washington Post. 18.02.2015.

А.Д. Каприн, Г.Р. Абузарова. Фармакотерапия онкологической боли в России. Реальность и перспективы // Материалы Международного медицинского конгресса «Паллиативная медицина в здравоохранении Российской Федерации и стран СНГ». 2014.

О.И. Усиенко. Проблемы доступности наркотических анальгетиков для лечения хронического болевого синдрома у инкурабельных онкологических больных. 2010. URL: http://www.pallcare.ru/ru/?p=news&id=1265443043 (дата обращения 12.01.2016).

HORIZON 2020 WORK PROGRAMME 2014-2015. Health, demographic change and wellbeing. European Commission. European Union. 2014.

Thomson Reuters Integrity. URL: http://ip-science.thomsonreuters.com/ pharma/integrity_whatsnew/ (дата обращения 10.10.2015).

Comparison Study of Liquid and Lyophilized Formulations of Subcutaneous Tetrodotoxin (TTX) in Healthy Volunteers. Wex Pharmaceuticals Inc. ClinicalTrials.gov Identifier: NCT01527734. 2012.

G. Varrassi. Severe chronic pain - the reality of treatment in Europe // Curr Med Res Opin. 2011. № 27(10). P. 2063-2064.

C. Buckenmaier, L. Bleckner. Military advanced regional anesthesia and analgesia handbook. - N.Y.: Borden Institute Government Printing Office, 2009. 316 p.

R. Thomas. Pain Management Task Force: Final Report. - NY: DIANE Publishing, 2011. 160 p.

L. Manchikanti, S. Helm 2nd, B. Fellows, J.W. Janata, V. Pampati, J.S. Grider, M.V. Boswell. Opioid epidemic in the United States // Pain Physician. 2012. №. 15(3). P. 9-38.

M. Mazer-Amirshahi, K. Dewey, P.M. Mullins. Trends in opioid analgesic use for headaches in US emergency departments // Am J Emerg Med. 2014. № 32(9). P. 1068-1073.

M. Mazer-Amirshahi, P.M. Mullins, I. Rasooly, J. van den Anker, J.M. Pines. Rising opioid prescribing in adult U.S. emergency department visits: 2001-2010 // Acad Emerg Med. 2014. № 21(3). P. 236-243.

M. Mazer-Amirshahi, Mullins, I.R. Rasooly, J. van den Anker, J.M. Pines. Trends in prescription opioid use in pediatric emergency department patients // Pediatr Emerg Care. 2014. № 30(4). P. 230-235.

H. Song, J. Li, C.L. Lu, L. Kang, L. Xie, Y.Y. Zhang, X.B. Zhou, S. Zhong. Tetrodotoxin alleviates acute heroin withdrawal syndrome: a multicentre, randomized, double-blind, placebo-controlled study // Clin Exp Pharmacol Physiol. 2011. № 38(8). P. 510-514.

J. Shi, T.T. Liu, X. Wang, D.H. Epstein, L.Y. Zhao, X.L. Zhang, L. Lu. Tetrodotoxin reduces cue-induced drug craving and anxiety in abstinent heroin addicts // Pharmacol Biochem Behav. 2009. № 92(4). P. 603-607.

(A) N. Hagen, K. Fisher, P. Du Souich, S. Chary, D. Moulin, E. Sellers. A multi-centre open-label, doseescalation study of intramuscular tetrodotoxin for severe cancer pain // 23rd Annu Sci Meet Am Pain Soc. Vancouver. May 6-9, 2004. Abst 304. (B) An open-label, multi-dose efficacy and safety study of intramuscular tetrodotoxin in patients with severe cancer-related pain // J Pain Symptom Manage. 2007. № 34(2). P. 171-182.

Tetrodotoxin is safe and effective for severe, refractory cancer pain // J Support Oncol. 2004. № 2(1). P. 18.

M.-O. Parat. Morphine and Metastasis. - Springer Science & Business Media, 2012. Р. 151.

A. Hoehne, D. Behera, W.H. Parsons. A 18F-labeled saxitoxin derivative for in vivo PET-MR imaging of voltage-gated sodium channel expression following nerve injury // J Am Chem Soc. 2013. № 135(48). P. 18012-18015.

Патент WO 2010129864 A2. Methods and compositions for studying, imaging, and treating pain. 2010.

R. Sakai, G.T. Swanson. Recent Progress in Neuroactive Marine Natural Products // Nat Prod Rep. 2014. № 31(2). P. 273-309.

F. Zhang, X. Xu, T. Li, Zh. Liu. Shellfish Toxins Targeting Voltage-Gated Sodium Channels // Mar. Drugs. 2013. V. 11. P. 4698-4723.

Патент US 8377951. N.A. Wilson. Transdermal administration of phycotoxins. 2013.

G. Kuthiala, G. Chaudhary. Ropivacaine: A review of its pharmacology and clinical use // Indian J Anaesth. 2011. № 55(2). P. 104-110.

S.J. Bajwa, J. Kaur. Clinical profile of levobupivacaine in regional anesthesia: A systematic review // J Anaesthesiol Clin Pharmacol. 2013. № 29(4). P. 530-539.

A.J. Rodrı´guez-Navarro, Ch.B. Berde, G. Wiedmaier. Comparison of Neosaxitoxin Versus Bupivacaine via Port Infiltration for Postoperative Analgesia Following Laparoscopic Cholecystectomy // Regional Anesthesia and Pain Medicine. 2011. № 2. V. 36.

A.J. Rodriguez-Navarro, N. Lagos, M. Lagos, I. Braghetto, A. Csendes. Neosaxitoxin as a local anesthetic: preliminary observations from a first human trial // Anesthesiology. 2007. № 106(2). P. 339-345.

F.R. Nieto, E.J. Cobos, M.Á. Tejada, C. Sánchez-Fernández, R. González-Cano, C.M. Cendán. Tetrodotoxin (TTX) as a Therapeutic Agent for Pain // Mar Drugs. 2012. № 10(2). P. 281-305.

E.G. Moczydlowski. The molecular mystique of tetrodotoxin // Toxicon. 2013. № 63. P. 165-183.

A. Nardi, N. Damann, T. Hertrampf, A. Kless. Advances in Targeting Voltage-Gated Sodium Channels with Small Molecules // ChemMedChem. Special Issue: Ion Channel Drug Discovery. 2012. V. 7. Is. 10. P. 1712-1740.

A.R. Harmer, J.-P. Valentin, C.E. Pollard. On the relationship between block of the cardiac Na+ channel and drug-induced prolongation of the QRS complex // British Journal of Pharmacology. 2011. V. 164. Is. 2.

H. Zhang. Validation of IonWorks Quattro Assays for Screening of State-Dependent Nav1.7 Blockers // Neuroscience Discovery. 2008. URL: http://www.aurorabiomed.com/download/presentations/HowardZhang.pdf (дата обращения 12.01.2016).

Sh.-W. Yang, G.D. Ho, D. Tulshian. Bioavailable pyrrolo-benzo-1,4-diazines as Nav1.7 sodium channel blockers for the treatment of pain // Bioorg. Med. Chem. Lett. 2014. № 24. P. 4958-4962.

S.K.G. Maier, R.E. Westenbroek, K.A. Schenkman. An unexpected role for brain-type sodium channels in coupling of cell surface depolarization to contraction in the heart // PNAS. 2002. № 6. V. 99. P. 4073-4078.

(A) G.P. Rossini. Toxins and Biologically Active Compounds from Microalgae: Biological Effects and Risk Management, т. 1. - NY: CRC Press, 2014. 542 р. (B) Gian Paolo Rossini. Toxins and Biologically Active Compounds from Microalgae: Biological Effects and Risk Management, т. 2. - NY: CRC Press, 2014. 700 р.

W.J. Brackenbury. Voltage-gated sodium channels and metastatic disease. Channels 6:5. - Austin, US: Landes Bioscience, 2012. P. 352-361.

P.U. Onganer, M.B. Djamgoz. Small-cell lung cancer (human): potentiation of endocytic membrane activity by voltage-gated Na(+) channel expression in vitro // J. Membr. Biol. 2005. № 204. P. 67-75. URL: http://dx.doi.org/10.1007/s00232-005-0747-6 (дата обращения 12.01.2016).

S.P. Fraser, J.K. Diss, L.J. Lloyd, F. Pani, A.M. Chioni, A.J. George et al. T-lymphocyte invasiveness: control by voltage-gated Na+ channel activity // FEBS Lett. 2004. № 569. P. 191-194. URL: http://dx.doi.org/10.1016/j.febslet.2004.05.063 (дата обращения 12.01.2016).

S.P. Fraser, J.K. Diss, A.M. Chioni, M.E. Mycielska, H. Pan, R.F. Yamaci et al. Voltage-gated sodium channel expression and potentiation of human breast cancer metastasi // Clin Cancer Res. 2005. № 11. P. 5381-5389. URL: http://dx.doi.org/10.1158/1078-0432.CCR-05-0327 (дата обращения 12.01.2016).

D. Diaz, D.M. Delgadillo, E. Hernández-Gallegos, M.E. Ramírez-Domínguez, L.M. Hinojosa, C.S. Ortiz et al. Functional expression of voltage-gated sodium channels in primary cultures of human cervical cancer // J Cell Physiol. 2007. № 210. P. 469-478. URL: http://dx.doi.org/10.1002/jcp.20871 (дата обращения 12.01.2016).

G. Fulgenzi, L. Graciotti, M. Faronato, M.V. Soldovieri, F. Miceli, S. Amoroso et al. Human neoplastic mesothelial cells express voltage-gated sodium channels involved in cell motility // Int J Biochem Cell Biol. 2006. № 38. P. 1146-1159. URL: http://dx.doi.org/10.1016/j.biocel.2005.12.003 (дата обращения 12.01.2016).

S. Roger, J. Rollin, A. Barascu, P. Besson, P.I. Raynal, S. Iochmann et al. Voltage-gated sodium channels potentiate the invasive capacities of human nonsmallcell lung cancer cell lines // Int J Biochem Cell Biol. 2007. № 39. P. 774-786. URL: http://dx.doi.org/10.1016/j.biocel.2006.12.007 (дата обращения 12.01.2016).

R. Gao, Y. Shen, J. Cai, M. Lei, Z. Wang. Expression of voltage-gated sodium channel alpha subunit in human ovarian cancer // Oncol Rep. 2010. № 23. P. 1293-1299.

J.K. Diss, S.N. Archer, J. Hirano, S.P. Fraser, M.B. Djamgoz. Expression profiles of voltage-gated Na(+) channel alpha-subunit genes in rat and human prostate cancer cell lines // Prostate. 2001. № 48. P. 165-78. URL: http://dx.doi.org/10.1002/pros.1095 (дата обращения 12.01.2016).

E. Hernandez-Plata, C.S. Ortiz, B. Marquina-Castillo, I. Medina-Martinez, A. Alfaro, J. Berumen et al. Overexpression of NaV 1.6 channels is associated with the invasion capacity of human cervical cancer // Int J Cancer. 2012. № 130. P. 2013-2023. URL: http://dx.doi.org/10.1002/ijc.26210 (дата обращения 12.01.2016).

M.D. Carrithers, G. Chatterjee, L.M. Carrithers, R. Offoha, U. Iheagwara, C. Rahner et al. Regulation of podosome formation in macrophages by a splice variant of the sodium channel SCN8A // J Biol Chem. 2009. № 284. P. 8114-8126. URL: http://dx.doi.org/10.1074/jbc.M801892200 (дата обращения 12.01.2016).

C.D. House, C.J. Vaske, A.M. Schwartz, V. Obias, B. Frank, T. Luu et al. Voltage-gated Na+ channel SCN5A is a key regulator of a gene transcriptional network that controls colon cancer invasion // Cancer Res. 2010. № 70. P. 6957-6967. URL: http://dx.doi.org/10.1158/0008-5472.CAN-10-1169 (дата обращения 12.01.2016).

S.W. Ou, A. Kameyama, L.Y. Hao, M. Horiuchi, E. Minobe, W.Y. Wang et al. Tetrodotoxin-resistant Na+ channels in human neuroblastoma cells are encoded by new variants of Nav1.5/SCN5A // Eur J Neurosci. 2005. № 22. P. 793-801. URL: http://dx.doi.org/10.1111/j.1460-9568.2005.04280.x (дата обращения 12.01.2016).

J.K. Diss, D. Stewart, S.P. Fraser, J.A. Black, S. Dib-Hajj, S.G. Waxman et al. Expression of skeletal muscletype voltage-gated Na+ channel in rat and human prostate cancer cell lines // FEBS Lett. 1998. № 427. P. 5-10. URL: http://dx.doi.org/10.1016/S0014-5793(98)00378-0 (дата обращения 12.01.2016).

B. Shan, M. Dong, H. Tang1, N. Wang et al. Voltagegated sodium channels were differentially expressed in human normal prostate, benign prostatic hyperplasia and prostate cancer cells // Oncology Letters. 2014. № 8. P. 345-350.

H. Smith, S. Passik. Pain and Chemical Dependency. - Oxford: Oxford University Press, 2008. 448 с.

Сайт WEX Pharmaceuticals Inc. URL: www.wexpharma.com (дата обращения 15.10.2014).

J. Lago, L.P. Rodríguez, L. Blanco, J.M. Vieites, A.G. Cabado. Review Tetrodotoxin, an Extremely Potent Marine Neurotoxin: Distribution, Toxicity, Origin and Therapeutical Uses // Mar. Drugs. 2015. № 13. P. 6384-6406.

Ch.B. Berde, U. Athiraman, B. Yahalom, D. Zurakowski, G. Corfas, C. Bognet. Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia // Mar. Drugs. 2011. № 9. P. 2717-2728.

Патент US 8486901. Sodium channel blocking compounds tetrodotoxin galactopyranosides. Заявитель Wex Medical Limited. - Заявл. 26.06.12; опубл. 10.09.13.

V. Bane, M. Lehane, M. Dikshit et al. Tetrodotoxin: Chemistry, Toxicity, Source, Distribution and Detection // Toxins. 2014. № 6. P. 693-755.

The authors declare that there are no conflicts of interest present.