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281 ORIGINALNI RAD / ORIGINAL PAPER DOI 10.2298/VETGL1406281I UDC 57.085+615.222:616.12+599.1.3./.8.4. ISPITIVANJE ANTIARITMIJSKE AKTIVNOSTI NOVOSINTETISANIH '(5,9$7$ 3523$)(121$ 8 $.21,7,16.20 02'(/8 65þ$1( ARITMIJE KOD PACOVA* TESTING OF NEWLY SYNTHESIZED PROPAFENONE DERIVATIVES ANTIARRHYTHMIC ACTIVITY IN ACONITIC MODEL OF CARDIAC ARRHYTHMIA IN RATS ,YNRYLý %UDQND *RMNRYLý%XNDULFD /MLOMDQD 1RYDNRYLý 5DGPLOD üXSLý 9 9ODGLPLURY 6 åLYDQRYLý 9 ãýHSDQRYLý 5 Primenom akonitinskog testa, u in vivo eksperimentima na pa- covima u dubokoj anesteziji, ispitivan je antiaritmijski potencijal no- YRVLQWHWLVDQLK ÀXRULUDQLK GHULYDWD SURSDIHQRQD äLYRWLQMH VX SRGHO- MHQH X þHWLUL HNVSHULPHQWDOQH JUXSH 3UYD JUXSD DNRQLWLQVND JUXSD MH WUHWLUDQD DNRQLWLQRP X GR]L RG ȝJNJ WP NRMD GRYRGL GR YLG- QRJ SRUHPHüDMD VUþDQRJ ULWPD X NUDWNRP YUHPHQVNRP SHULRGX .DR SDUDPHWDU ]D UHJLVWURYDQMH SRUHPHüDMD VUþDQRJ ULWPD X]HWD MH SRMDYD YHQWULNXODUQH HNVWUDVLVWROH 9(6 2VWDOH WUL HNVSHULPHQWDOQH JUXSH þLQLOH VX åLYRWLQMH QD NRMLPD MH LVSLWLYDQ SRWHQFLMDO SURSDIHQRQD L ÀXR- ULUDQLK GHULYDWD SURSDIHQRQD GD ]DXVWDYH DULWPLMX LQGXNRYDQX LY LQ- MHNFLMRP DNRQLWLQD ȝJNJ WP 3URSDIHQRQ NDR L 2) GHULYDW QLVX XVSHOL GD NRQYHUWXMX SRUHPHüHQ VUþDQL ULWDP SUHåLYOMDYDQMH åLYRWLQMD MH 3ULOLNRP DSOLNDFLMH 3) GHULYDWD X GR]L RG PJNJ WP åLYRWL QMH VX SUHåLYHOH X] SRYUHPHQR XVSRVWDYOMDQMH VLQXVQRJ ULWPD .OMXþQH UHþL DQWLDULWPLFL DNRQLWLQVNL WHVW MRQVNL NDQDOL * Rad primljen za štampu 06. 12. 2013. godine 'U VF %UDQND ,YNRYLü GRFHQW 8QLYHU]LWHW X %HRJUDGX )DUPDFHXWVNL IDNXOWHW GU VF /MLOMDQD *RMNRYLü%XNDULFD UHG SURIHVRU PU VF 5DGPLOD 1RYDNRYLü ,QVWLWXW ]D IDUPDNRORJLMX NOLQLþNX IDUPDNRORJLMX L WRNVLNRORJLMX 0HGLFLQVNL IDNXOWHW 8QLYHU]LWHW X %HRJUDGX GU VF 9LWRPLU ûXSLü UHG SURIHVRU )DNXOWHW YHWHULQDUVNH PHGLFLQH 8QLYHU]LWHW X %HRJUDGX GU VF 6RWH 9ODGLPLURY UHG SURIHVRU )DUPDFHXWVNL IDNXOWHW 8QLYHU]LWHW X %HRJUDGX PU VF 9ODGLPLU äLYDQRYLü DVLV WHQW GU VF 5DGLVDY âüHSDQRYLü UHG SURIHVRU .%& ³'UDJLãD 0LãRYLü´ %HRJUDG
Transcript

281

ORIGINALNI RAD / ORIGINAL PAPER

DOI 10.2298/VETGL1406281I UDC 57.085+615.222:616.12+599.1.3./.8.4.

ISPITIVANJE ANTIARITMIJSKE AKTIVNOSTI NOVOSINTETISANIH

ARITMIJE KOD PACOVA* TESTING OF NEWLY SYNTHESIZED PROPAFENONE DERIVATIVES

ANTIARRHYTHMIC ACTIVITY IN ACONITIC MODEL OF

CARDIAC ARRHYTHMIA IN RATS

Primenom akonitinskog testa, u in vivo eksperimentima na pa-covima u dubokoj anesteziji, ispitivan je antiaritmijski potencijal no-

-

-

--

* Rad primljen za štampu 06. 12. 2013. godine

282

In-

ternational Nonproprietary Name

Ikr

kalijumskoj struji u srcu i hERG kanalu koji posreduje u njenom prenošenju. Ikr

-

ppression Trial

Figure 1. A. Phenylpropiophenone structure, B. Propafenone structural formula

283

WPW

u studije razvoja rezistencija na lekove

in silico metoda

sprovedeno je na pacovima soja Wistar

ad

libitum

je (

284

®

3 u koncentraciji od

što se

tave aritmiju indukovanu i.v. aplikacijom akonitina primenjen je akonitinski test

pari

285

kontinuirano se prati promena krvnog pritiska i na svakih 10 minuta registruje na

skog pritiska.

zatim na svaki minut sve do uspostavljanja sinusnog ritma 60 minuta od aplikaci

rigora mortis

A B

Figure 2. ECG of rats (II drain) a) normal sinus rhythm before aconitine application; b) appearance of ventricular extrasystoles induced by i.v. aconitine injection

286

/

Table 1. Time and percentage of survival of animals during the investigation on therapeutic role of propafenone, 5OF and 5PF derivatives

5OF

5OF

5PF

4 mg/kg

6 mg/kg

287

tip 1.5 u srcu opravdana je primena akonitinskog testa u ispitivanju antiaritmijskog

potencijala sintetisanih derivata.

U eksperimentalnim modelima aritmije za hemijsku indukciju aritmije uglav

temperaturom od 37 1 C.

4 mg/kg t.m. nedovoljna da zaustavi aritmiju indukovanu akonitinom ili doza ako

aplikacije ispitivanog jedinjenja i akonitinaFigure 3. a) Changes in heart rate in all the groups in regard to propafenone one, concerning all the three tested

doses (1)-dose 6 mg/kg; (2)-dose 4 mg/kg and (3)-dose 2 mg/kg, b) record of the rats blood pressure, before, during and after application of the tested compound and aconitine

288

v

in vitro ispitivanjima antagonizovao

in vivo eksperimentima ispitivan je antiarit

ACKNOWLEDGEMENT:

tokom ove studije. /

-

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

Conclusion

289

11.

12.

13.

14.

2006.

TESTING OF NEWLY SYNTHESIZED PROPAFENONE DERIVATIVES ANTIARRHYTHMIC ACTIVITY IN ACONITIC MODEL OF CARDIAC ARRHYTHMIA

IN RATS

ENGLISH

290

in vivo


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