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Benzodiazepine receptors mediated anxiolytic-like effects of some 1,3,5-triaryl-4,5-dihydro-1h-pyrazole derivatives

Year 2016, Volume: 41 Issue: 2, 304 - 315, 30.06.2016
https://doi.org/10.17826/cutf.208627

Abstract

Purpose: Pyrazole is a heterocycle structure characterized by a five-membered ring of three carbon and two adjacent nitrogen atoms. Numerous compounds including pyrazole nucleus have been reported to possess wide diverse of pharmacological activities related to central nervous system. Based on this knowledge, in the present study, we planned to examine probable anxiolytic-like effects of eighteen 1,5-diaryl-3-[4-(methylsulfonyl)phenyl]-4,5-dihydro-1H-pyrazole derivative test compounds (2a-s) which previously synthesized by our research group.
Material and Methods: Anxiolytic activity potential of the test compounds (100 mg/kg, i.p) was evaluated in mice using hole-board and plus-maze tests. An antagonism study was conducted with flumazenil (3 mg / kg, ip), a GABA-benzodiazepine receptor blocker, in order to investigate mechanism of the anxiolytic-like activities.
Results: In the hole-board tests, compounds 2g, 2h, 2k and 2s significantly increased total number of the head-dipping behavior and number of the explored holes. In the plus-maze tests, the same compounds increased the time spent in the open arms and the number of entries into the open arms. These findings indicated that these four compounds have anxiolytic-like effects. Reference drug diazepam (1 mg/kg, i.p) also showed its anxiolytic activity in both of the tests, as expected. 
Conclusion: Benzodiazepine receptors mediated the anxiolytic-like effects of 2g, 2h, 2k and 2s coded 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivative compounds.

References

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  • Oliveira S, Pizzuti L, Quina F, Flores A, Lund R, Lencina C et al. Anti-candida, anti-enzyme activity and cytotoxicity of 3,5-diaryl-4,5-dihydro-1H- pyrazole-1-carboximidamides. 2014;19:5806-20. Molecules.
  • Zhao MY, Yin Y, Yu XW, Sangani CB, Wang SF, Lu AM et al. Synthesis, biological evaluation and 3D- QSAR study of novel 4,5-dihydro-1H-pyrazole thiazole derivatives as BRAF(V⁶⁰⁰E) inhibitors. Bioorg Med Chem. 2015;23:46-54.
  • Amir M, Kumar H, Khan SA. Synthesis and pharmacological evaluation of pyrazoline derivatives as new anti-inflammatory and analgesic agents. Bioorg Med Chem Lett. 2008;18:918-22.
  • Milano J, Oliveira SM, Rossato MF, Sauzem PD, Machado P, Beck P et al. Antinociceptive effect of novel trihalomethyl-substituted pyrazoline methyl esters in formalin and hot-plate tests in mice. Eur J Pharmacol. 2008;581:86-96.
  • Milano J, Rossato MF, Oliveira SM, Drewes C, Machado P, Beck P et al. Antinociceptive action of 4-methyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro- 1H-pyrazole methyl ester in models of inflammatory pain in mice. Life Sci. 2008;83:739-46
  • Kaplancikli ZA, Turan-Zitouni G, Ozdemir A, Can Ov, Chevallet P. Synthesis and antinociceptive activities of some pyrazoline derivatives. Eur J Med Chem. 2009;44:2606-10.
  • Khode S, Maddi V, Aragade P, Palkar M, Ronad PK, Mamledesai S et al. Synthesis and pharmacological evaluation of a novel series of 5-(substituted)aryl-3- (3-coumarinyl)-1-phenyl-2-pyrazolines as novel anti- inflammatory and analgesic agents. Eur J Med Chem. 2009;44:1682-8.
  • Demir Özkay U, Can OD, Kaplancıklı ZA. Antinociceptive activities of some triazole and pyrazoline moieties-bearing compounds. Med Chem Res. 2012;21:1056-61.
  • Bandgar BP, Adsul LK, Chavan HV, Jalde SS, Shringare SN, Shaikh R et al. Synthesis, biological evaluation, and docking studies of 3-(substituted)- aryl-5-(9-methyl-3-carbazole)-1H-2-pyrazolines potent anti-inflammatory and antioxidant agents. Bioorg Med Chem Lett. 2012;22:5839-44. as
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  • Pasin JS, Ferreira AP, Saraiva AL, Ratzlaff V, Andrighetto R, Machado P et al. Antipyretic and antioxidant activities of 5-trifluoromethyl-4,5- dihydro-1H-pyrazoles in rats. Braz J Med Biol Res. 2010;43:1193-202.
  • Buschmann H, Christoph T, Friderichs E, Maul C, Sundermann, B. Analgesics: From Chemistry and Pharmacology to Clinical Application, Weinheim: Published by Wiley-VCH, 2002.
  • Rx Media Pharma®. İnterAktif İlaç Bilgi Kaynağı, 2015.
  • Can OD, Ozkay UD, Kaplancıklı ZA., Ozturk Y. Effects of some 1,3,5-trisubstitued-2-pyrazoline derivatives on depression and anxiety parameters of mice. Arch Pharm Res. 2009;32:1293-9.
  • Gökhan-Kelekçi N, Koyunoğlu S, Yabanoğlu S, Yelekçi K, Ozgen O, Uçar G et al. New pyrazoline bearing monoamine oxidase: synthesis, biological evaluation, and structural determinants of MAO-A and MAO-B selectivity. Bioorg Med Chem. 2009;17:675-89.
  • Kaplancikli ZA, Ozdemir A, Turan-Zitouni G, Altıntop MD, Can OD. New pyrazoline derivatives and their antidepressant activity. Eur J Med Chem. 2010;45:4383-7.
  • Koç GŞ, Tan OU, Uçar G, Yildirim E, Erol K, Palaska E., Synthesis and monoamine oxidase inhibitory activities of some 3-(4-fluorophenyl)-5- aryl-n-substituted-4,5-dihydro-(1H)-pyrazole-1- carbothioamide derivatives. Drug Res (Stuttg). 2014;64:591-8.
  • Mathew B, Suresh J, Anbazghagan S, Dev S. Molecular docking studies of some novel antidepressant 5-substituted phenyl-3-(thiophen-2- yl)-4,5-dihydro-1H-pyrazole-1-carboxamides against monoamine oxidase isoforms. Cent Nerv Syst Agents Med Chem 2015 (in press).
  • Özdemir Z, Kandilci HB, Gümüşel B, Caliş U, Bilgin AA. Synthesis and studies on antidepressant and anticonvulsant activities of some 3-(2-furyl)- pyrazoline derivatives. Eur J Med Chem. 2007;42:373-9.
  • Palaska E, Aytemir M, Uzbay IT, Erol D. Synthesis and antidepressant activities of some 3,5-diphenyl-2- pyrazolines. Eur J Med Chem. 2001;36:539-43.
  • Özdemir A, Altıntop MD, Kaplancıklı ZA, Can ÖD, Demir Özkay Ü, Turan-Zitouni G. Synthesis and evaluation sulfonyl)phenyl]-4,5-dihydro-1H-pyrazole derivatives as potential antidepressant agents. Molecules. 2015;20:2668-84.
  • ,5-diaryl-3-[4-(methyl
  • Aboul-Enein MN, El-Azzouny AA, Attia MI, Maklad YA, Amin KM, Abdel-Rehim M et al. Design and synthesis of novel stiripentol analogues as potential anticonvulsants. Eur J Med Chem. 2012;47:360-9.
  • Güniz Küçükgüzel S, Rollas S, Erdeniz H, Kiraz M, Cevdet Ekinci A, Vidin A. Synthesis, characterization and pharmacological properties of some 4- arylhydrazono-2-pyrazoline-5-one obtained from heterocyclic amines. Eur J Med Chem. 2000;35:761-71. derivatives
  • Singh SP, Chaudhari A, Barthwal JP, Parmar SS. Anticonvulsant activity and selective inhibition of nicotinamide oxidations by 1,3,5-trisubstituted pyrazolines. J Pharm Sci. 1974;63:1948-50.
  • dinucleotide-dependent
  • Nakagawa T., Ozawa T., Shige K., Yamamoto R., Minami M., Satoh M. Inhibition of morphine tolerance and dependence by MS-153, a glutamate transporter activator. Eur J Pharmacol. 2001;419:39- 45.
  • Shimada F, Shiga Y, Morikawa M, Kawazura H, Morikawa O, Matsuoka T et al. The neuroprotective agent MS-153 stimulates glutamate uptake. Eur J Pharmacol. 1999;336:263-70.
  • Yamashita H, Okumura K, Lizuka H, Ohto N. Process for producing 1-acyl-2-pyrazolines for treatment of cerebral edema. Eur Pat Appl EP 322,691. C.A. 112 1990; 98520.
  • Godoy MC, Fighera MR, Souza FR, Flores AE, Rubin MA, Oliveira MR et al. Alpha 2-adrenoceptors and 5-HT receptors mediate the antinociceptive effect of new pyrazolines, but not of dipyrone. Eur J Pharmacol. 2004;496:93-7.
  • Tortorici V, Vanegas H. Putative role of medullary off- and on-cells in the antinociception produced by dipyrone (metamizol) administered systemically or microinjected into PAG. Pain. 1994;57:197-205.
  • Can ÖD, Alyu F, Turan N, Özdemir A. Antinociceptive activities of some 4,5-dihydro-1H- pyrazole derivatives: involvement of central and peripheral pathways. Lett Drug Des Discov 2016 (in press). 34. File SE, Pellow S. triazolobenzodiazepines in two animal tests of anxiety and in the holeboard. British J Pharmacol 1985;86:729-35. The effects of
  • Can OD, Ozkay UD, Oztürk N, Oztürk Y. Effects of hawthorn seed and pulp extracts on the central nervous system. Pharm Biol. 2010;48:924-31.
  • Can OD, Demir Özkay, Ü. Effects of Hypericum montbretti extract on the central nervous system and involvement receptors in its pharmacological activity. Phytother Res. 2012;26:1695-700. (A)/benzodiazepine
  • Takeda H, Tsuji M, Matsumiya T. Changes in head- dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice. Eur J Pharmacol. 1998;350:21-9.
  • Can OD, Demir Özkay U, Kıyan HT, Demirci B. Psychopharmacological profile of Chamomile (Matricaria recutita L.) essential oil in mice. Phytomedicine. 2012;19:306-10.
  • Peng WH, Hsieh MT, Lee YS, Lin YC, Liao J. Anxiolytic effect of seed of Ziziphus jujuba in mouse models of anxiety. J Ethnopharmacol. 2000;72:435- 41.
  • Rejón-Orantes J del C, González-Esquinca AR, de la Mora MP, Roldan Roldan G, Cortes D. Annomontine, an alkaloid isolated from Annona purpurea, has anxiolytic-like effects in the elevated plus-maze. Planta Med. 2011;77:322-7.
  • Sampath C, Holbik M, Krenn L, Butterweck V. Anxiolytic effects of fractions obtained from Passiflora incarnata L. in the elevated plus-maze in mice. Phytother Res. 2011;25:789-95.
  • Salzman C, Miyawaki EK, le Bars P, Kerrihard TN. Neurobiologic basis of anxiety and its treatment. Harv Rev Psychiatry. 1993;1:197-206.

1,3,5-triaril-4,5-dihidro-1h-pirazol türevi bazı bileşiklerin benzodiazepin reseptörleri aracılıklı anksiyolitik-benzeri etkileri

Year 2016, Volume: 41 Issue: 2, 304 - 315, 30.06.2016
https://doi.org/10.17826/cutf.208627

Abstract

Amaç: Pirazol, üç karbon atomundan ve yan yana iki azot atomundan oluşan beş üyeli heterosiklik bir halka sistemidir. Literatürde pirazol çekirdeği taşıyan kimyasal bileşiklerin santral sinir sistemi üzerinde önemli bir etkinlik potansiyeli olduğuna ilişkin çok sayıda çalışmaya rastlamak mümkündür. Bu bilgiden hareketle, bu çalışmada, araştırma grubumuz tarafından sentezlenmiş olan onsekiz adet 1,5-diaril-3- [4- (metilsülfonil) fenil] -4,5-dihidro-1H-pirazol türevi bileşiğin (2a-s) olası ankiyolitik-benzeri aktiviteleri yönünden araştırılması planlanmıştır. 
Gereç ve Yöntem: Test bileşiklerinin (100 mg/kg, ip) anksiyolitik aktivite potansiyelleri, farelerde, delikli tahta ve yükseltilmiş artı-labirent testleri ile değerlendirilmiştir. Anksiyolitik-benzeri etkinliğe aracılık eden mekanizmaları araştırmak üzere GABA-A benzodiazepin reseptör blokörü flumazenil (3 mg/kg, i.p) ile antagonizma çalışması yapılmıştır.
Bulgular: Serideki 2g, 2h, 2k ve 2s kodlu bileşikler, farelerin delikli tahta testlerinde ölçülen toplam baş daldırma ve keşfedilen delik sayılarını anlamlı olarak artırmıştır. Aynı bileşikler, yükseltilmiş artı-labirent testi uygulanan farelerin hem açık kola giriş sayılarını hem de açık kolda kalma sürelerini anlamlı biçimde artırmıştır. Bu bulgular, söz konusu dört bileşiğin anksiyolitik-benzeri etkilere sahip olduğunu ortaya koymuştur. Diğer yandan, referans ilaç olarak kullanılan diazepam (1 mg / kg, ip) da hem delikli tahta hem de yükseltilmiş artı-labirent testlerinde beklenen anksiyolitik aktiviteyi göstermiştir. Sonuç: 2g, 2h, 2k ve 2s kodlu 1,3,5-triaril-4,5-dihidro-1H-pirazol türevlerinin anksiyolitik-benzeri etkilerine benzodiazepin reseptörleri aracılık etmektedir.

References

  • Goodell JR, Puig-Basagoiti F, Forshey BM, Shi PY, Ferguson DM. Identification of compounds with anti-West Nile virus activity. J Med Chem. 2006;49:2127-37.
  • Liu JJ, Sun J, Fang YB, Yang YA, Jiao RH, Zhu HL. Synthesis, and antibacterial activity of novel 4,5- dihydro-1H-pyrazole derivatives as DNA gyrase inhibitors. Org Biomol Chem. 2014;12:998-1008.
  • Oliveira S, Pizzuti L, Quina F, Flores A, Lund R, Lencina C et al. Anti-candida, anti-enzyme activity and cytotoxicity of 3,5-diaryl-4,5-dihydro-1H- pyrazole-1-carboximidamides. 2014;19:5806-20. Molecules.
  • Zhao MY, Yin Y, Yu XW, Sangani CB, Wang SF, Lu AM et al. Synthesis, biological evaluation and 3D- QSAR study of novel 4,5-dihydro-1H-pyrazole thiazole derivatives as BRAF(V⁶⁰⁰E) inhibitors. Bioorg Med Chem. 2015;23:46-54.
  • Amir M, Kumar H, Khan SA. Synthesis and pharmacological evaluation of pyrazoline derivatives as new anti-inflammatory and analgesic agents. Bioorg Med Chem Lett. 2008;18:918-22.
  • Milano J, Oliveira SM, Rossato MF, Sauzem PD, Machado P, Beck P et al. Antinociceptive effect of novel trihalomethyl-substituted pyrazoline methyl esters in formalin and hot-plate tests in mice. Eur J Pharmacol. 2008;581:86-96.
  • Milano J, Rossato MF, Oliveira SM, Drewes C, Machado P, Beck P et al. Antinociceptive action of 4-methyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro- 1H-pyrazole methyl ester in models of inflammatory pain in mice. Life Sci. 2008;83:739-46
  • Kaplancikli ZA, Turan-Zitouni G, Ozdemir A, Can Ov, Chevallet P. Synthesis and antinociceptive activities of some pyrazoline derivatives. Eur J Med Chem. 2009;44:2606-10.
  • Khode S, Maddi V, Aragade P, Palkar M, Ronad PK, Mamledesai S et al. Synthesis and pharmacological evaluation of a novel series of 5-(substituted)aryl-3- (3-coumarinyl)-1-phenyl-2-pyrazolines as novel anti- inflammatory and analgesic agents. Eur J Med Chem. 2009;44:1682-8.
  • Demir Özkay U, Can OD, Kaplancıklı ZA. Antinociceptive activities of some triazole and pyrazoline moieties-bearing compounds. Med Chem Res. 2012;21:1056-61.
  • Bandgar BP, Adsul LK, Chavan HV, Jalde SS, Shringare SN, Shaikh R et al. Synthesis, biological evaluation, and docking studies of 3-(substituted)- aryl-5-(9-methyl-3-carbazole)-1H-2-pyrazolines potent anti-inflammatory and antioxidant agents. Bioorg Med Chem Lett. 2012;22:5839-44. as
  • Bano S, Javed K, Ahmad S, Rathish IG, Singh S, Alam MS. Synthesis and biological evaluation of some sulfonamide moiety as potential anti-inflammatory and anti-cancer agents. Eur J Med Chem. 2011;46:5763-8. bearing benzene
  • Rathish IG, Javed K, Ahmad S, Bano S, Alam MS, Pillai KK et al. Synthesis and antiinflammatory activity of some new 1,3,5-trisubstituted pyrazolines bearing benzene sulfonamide. Bioorg Med Chem Lett. 2009;19:255-8.
  • Pasin JS, Ferreira AP, Saraiva AL, Ratzlaff V, Andrighetto R, Machado P et al. Antipyretic and antioxidant activities of 5-trifluoromethyl-4,5- dihydro-1H-pyrazoles in rats. Braz J Med Biol Res. 2010;43:1193-202.
  • Buschmann H, Christoph T, Friderichs E, Maul C, Sundermann, B. Analgesics: From Chemistry and Pharmacology to Clinical Application, Weinheim: Published by Wiley-VCH, 2002.
  • Rx Media Pharma®. İnterAktif İlaç Bilgi Kaynağı, 2015.
  • Can OD, Ozkay UD, Kaplancıklı ZA., Ozturk Y. Effects of some 1,3,5-trisubstitued-2-pyrazoline derivatives on depression and anxiety parameters of mice. Arch Pharm Res. 2009;32:1293-9.
  • Gökhan-Kelekçi N, Koyunoğlu S, Yabanoğlu S, Yelekçi K, Ozgen O, Uçar G et al. New pyrazoline bearing monoamine oxidase: synthesis, biological evaluation, and structural determinants of MAO-A and MAO-B selectivity. Bioorg Med Chem. 2009;17:675-89.
  • Kaplancikli ZA, Ozdemir A, Turan-Zitouni G, Altıntop MD, Can OD. New pyrazoline derivatives and their antidepressant activity. Eur J Med Chem. 2010;45:4383-7.
  • Koç GŞ, Tan OU, Uçar G, Yildirim E, Erol K, Palaska E., Synthesis and monoamine oxidase inhibitory activities of some 3-(4-fluorophenyl)-5- aryl-n-substituted-4,5-dihydro-(1H)-pyrazole-1- carbothioamide derivatives. Drug Res (Stuttg). 2014;64:591-8.
  • Mathew B, Suresh J, Anbazghagan S, Dev S. Molecular docking studies of some novel antidepressant 5-substituted phenyl-3-(thiophen-2- yl)-4,5-dihydro-1H-pyrazole-1-carboxamides against monoamine oxidase isoforms. Cent Nerv Syst Agents Med Chem 2015 (in press).
  • Özdemir Z, Kandilci HB, Gümüşel B, Caliş U, Bilgin AA. Synthesis and studies on antidepressant and anticonvulsant activities of some 3-(2-furyl)- pyrazoline derivatives. Eur J Med Chem. 2007;42:373-9.
  • Palaska E, Aytemir M, Uzbay IT, Erol D. Synthesis and antidepressant activities of some 3,5-diphenyl-2- pyrazolines. Eur J Med Chem. 2001;36:539-43.
  • Özdemir A, Altıntop MD, Kaplancıklı ZA, Can ÖD, Demir Özkay Ü, Turan-Zitouni G. Synthesis and evaluation sulfonyl)phenyl]-4,5-dihydro-1H-pyrazole derivatives as potential antidepressant agents. Molecules. 2015;20:2668-84.
  • ,5-diaryl-3-[4-(methyl
  • Aboul-Enein MN, El-Azzouny AA, Attia MI, Maklad YA, Amin KM, Abdel-Rehim M et al. Design and synthesis of novel stiripentol analogues as potential anticonvulsants. Eur J Med Chem. 2012;47:360-9.
  • Güniz Küçükgüzel S, Rollas S, Erdeniz H, Kiraz M, Cevdet Ekinci A, Vidin A. Synthesis, characterization and pharmacological properties of some 4- arylhydrazono-2-pyrazoline-5-one obtained from heterocyclic amines. Eur J Med Chem. 2000;35:761-71. derivatives
  • Singh SP, Chaudhari A, Barthwal JP, Parmar SS. Anticonvulsant activity and selective inhibition of nicotinamide oxidations by 1,3,5-trisubstituted pyrazolines. J Pharm Sci. 1974;63:1948-50.
  • dinucleotide-dependent
  • Nakagawa T., Ozawa T., Shige K., Yamamoto R., Minami M., Satoh M. Inhibition of morphine tolerance and dependence by MS-153, a glutamate transporter activator. Eur J Pharmacol. 2001;419:39- 45.
  • Shimada F, Shiga Y, Morikawa M, Kawazura H, Morikawa O, Matsuoka T et al. The neuroprotective agent MS-153 stimulates glutamate uptake. Eur J Pharmacol. 1999;336:263-70.
  • Yamashita H, Okumura K, Lizuka H, Ohto N. Process for producing 1-acyl-2-pyrazolines for treatment of cerebral edema. Eur Pat Appl EP 322,691. C.A. 112 1990; 98520.
  • Godoy MC, Fighera MR, Souza FR, Flores AE, Rubin MA, Oliveira MR et al. Alpha 2-adrenoceptors and 5-HT receptors mediate the antinociceptive effect of new pyrazolines, but not of dipyrone. Eur J Pharmacol. 2004;496:93-7.
  • Tortorici V, Vanegas H. Putative role of medullary off- and on-cells in the antinociception produced by dipyrone (metamizol) administered systemically or microinjected into PAG. Pain. 1994;57:197-205.
  • Can ÖD, Alyu F, Turan N, Özdemir A. Antinociceptive activities of some 4,5-dihydro-1H- pyrazole derivatives: involvement of central and peripheral pathways. Lett Drug Des Discov 2016 (in press). 34. File SE, Pellow S. triazolobenzodiazepines in two animal tests of anxiety and in the holeboard. British J Pharmacol 1985;86:729-35. The effects of
  • Can OD, Ozkay UD, Oztürk N, Oztürk Y. Effects of hawthorn seed and pulp extracts on the central nervous system. Pharm Biol. 2010;48:924-31.
  • Can OD, Demir Özkay, Ü. Effects of Hypericum montbretti extract on the central nervous system and involvement receptors in its pharmacological activity. Phytother Res. 2012;26:1695-700. (A)/benzodiazepine
  • Takeda H, Tsuji M, Matsumiya T. Changes in head- dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice. Eur J Pharmacol. 1998;350:21-9.
  • Can OD, Demir Özkay U, Kıyan HT, Demirci B. Psychopharmacological profile of Chamomile (Matricaria recutita L.) essential oil in mice. Phytomedicine. 2012;19:306-10.
  • Peng WH, Hsieh MT, Lee YS, Lin YC, Liao J. Anxiolytic effect of seed of Ziziphus jujuba in mouse models of anxiety. J Ethnopharmacol. 2000;72:435- 41.
  • Rejón-Orantes J del C, González-Esquinca AR, de la Mora MP, Roldan Roldan G, Cortes D. Annomontine, an alkaloid isolated from Annona purpurea, has anxiolytic-like effects in the elevated plus-maze. Planta Med. 2011;77:322-7.
  • Sampath C, Holbik M, Krenn L, Butterweck V. Anxiolytic effects of fractions obtained from Passiflora incarnata L. in the elevated plus-maze in mice. Phytother Res. 2011;25:789-95.
  • Salzman C, Miyawaki EK, le Bars P, Kerrihard TN. Neurobiologic basis of anxiety and its treatment. Harv Rev Psychiatry. 1993;1:197-206.
There are 43 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Research
Authors

Özgür Can

Nazlı Turan This is me

Feyza Alyu This is me

Publication Date June 30, 2016
Published in Issue Year 2016 Volume: 41 Issue: 2

Cite

MLA Can, Özgür et al. “1,3,5-Triaril-4,5-Dihidro-1h-Pirazol türevi Bazı bileşiklerin Benzodiazepin reseptörleri aracılıklı Anksiyolitik-Benzeri Etkileri”. Cukurova Medical Journal, vol. 41, no. 2, 2016, pp. 304-15, doi:10.17826/cutf.208627.