Farelerde Pentilentetrazol ve Striknin ile Oluşturulan Konvülsiyonlar Üzerinde 7-Nitro İndazolün Etkisi

Yıl 1996, Cilt: 1 Sayı: 1, 19 - 21, 30.11.1996

Faruk Erden Güner Ulak Esin Göldeli Nejat Gacar

Öz

Amaç:
Nitrik oksidin (NO) santral fizyolojik olaylarda, hücrereler arası bir haberci
olarak rolü olduğuna dair çeşitli kanıtlar mevcuttur. Çeşitli deneysel konvülsiyon
modellerinde nitrik oksid etkisiz, prokonvülsan veya antikonvülsan olarak
bildirilmektedir. Bu çalışmada beyindeki nitrik oksid sentaz (NOS) tipine
spesifik bir inhibitor olan 7-nitro indazolün (7-Nj), striknin (ST) ve
pentilentetrazol (PIZ) konvülsiyonları üzerindeki etkisini araştırmayı planladık.

Yöntem:
Subkütan (SK) ı.5 mg/kg ST veya 85 mg/kg PTZ verilerek; ilk miyoklonik spazm
(jMS), toplam konvülsiyon süresi, ölüm zamanı ve ölüm oranları saptandı. 7 Nİ,
AO veya serum fizyolojik (0. 1 ml/ 25gr) ST veya PTZ uygulamasından 30 dk önce
intraperitoneal olarak uygulandı. 7-Nİ intraperitoneal (i.p.) kullanım için
yerfıstığı yağıında (arachis oil, AO; peanut oil) çözüldü.

Bulgular:
7-Ni (30 mg/kg) her iki tip konvülsiyon modelindeki tüm parametreler üzerinde
etkisiz bulundu. Ancak AO ve SF alan fareler karşılaştırıldığında AO, ST
gruplarında tüm parametreleri, PTZ gruplarında ise sadece İMS'ı anlamlı olarak
uzattı (p < 0,05).

Sonuç:
Bu sonuç muhtemelen i.p. verilen yerfıstığı yağının, daha sonra SK. verilen ST
ve PTZ 'ün absorpsiyon ve/veya dağılım özelliklerini etkilemiş olabileceğini
akla getirmektedir. Sonuç olarak çalışmamızda kullanılan doz ve doz aralığında,
7-Nİ bu tip konvülsiyonlar üzerinde etkisiz görülmektedir. 

Anahtar Kelimeler

Nitrik oksid, 7-nitro indazol, striknin, pentilentetrazol

The Effect of 7-Nitro Indazole on Strychnine and Pentylenetetrazole-Induced Seizures in Mice

Öz

Objective:
There are some strong evidence about the role of nitric oxide (NO) as an
intercellular messenger in the central physiological mechanisms. It is
suggested that NO might be anticonvulsant, proconvulsant or ineffective on seizure
activity in various experimental seizure models. In this study, the effects of
7-nitro indazole (7-NI), a selective inhibitor for the form of nitric oxide
synthase enzyme found in the brain, on strychnine (ST) and pentylenetetrazole
(PTZ) induced seizures in mice were investigated.

Methods:
ST (1.5 mg/kg) or PTZ (85 mg/kg) were administered subcutaneously (s.c.) to
produce seizures. 7-NI, vehicle or saline (0. ı ml/25g, i.p.) were given 30
minutes prior to ST or PTZ to separate mice groups. 7-NI(30mg/kg) was dissolved
in arachis oil (AO; peanut oil) for intraperitoneal (i.p.) administration.

Results:
The first myoclonic jerk (FMJ), the total convulsion time (TCT), the survival
time, and the rate of mortality was recorded. 7-NI had no effect on all
parameters, both in ST and PıZ induced seizures. Interestingly AO compared to
saline controls significantly delayed FMJ and survival time; increased TCT;
decreased the rate of mortality induced by ST (p < 0.05). AO also
significantly delayed FMJ induced by PTZ compared to saline controls.

Conclusion:
 It is very possible that the i.p.
injection of AO could have altered absorption and/or distribution of the
subsequent s.c. injection of ST or PTZ. These observations suggested that 7-NI,
at dose and time intervals used in this study, had no effect on seizure
activity.

Anahtar Kelimeler

nitric oxide, 7-nitro indazole, strychinine, pentylenetetrazole

Kaynakça

• Buisson A, Lakhmeche N, Verrecchia C, Plotkine M, Boul, RG. Nitric oxide: an endogenous anticonvulsant substance. Neuroreport. 1993;4(4):444-446.
• Wallis RA, Panizzon KL, Henry D, Wasterlain CG. Neuroprotection against nitric oxide injury with inhibitors of ADP-ribosylation. Neuroreport. 1993;5(3):245-248.
• Williams MB, Li X, Gu X. Jope RS, Modulation of endogenous ADP-ribosylation in rat brain. Brain Res. 1992;592:49-56. doi:10.1016/0006-8993(92)91657-z
• East S J, Garthwaite J. NMDA receptor activation in rat hippocampus induces cyclic GMP formation through the L-arginine-nitric oxide pathway. Neuroscience letters. 1991;123(1):17-19.
• Kehne JH, Gallager DW, Davis M. Strychnine: brainstem and spinal mediation of excitatory effects on acoustic startle. European journal of pharmacology. 1981;76(2-3):177-186. doi:10.1016/0014-2999(81)90499-4
• Chavoix C, Hantraye P, Brouillet E, et al. Status epilepticus induced by pentylenetetrazole modulates in vivo [11C] Ro 15-1788 binding to benzodiazepine receptors. Effects of ligands acting at the supramolecular receptor complex. European journal of pharmacology. 1988;146(2-3):207-214. doi:10.1016/0014-2999(88)90294-4
• MacKenzie GM, Rose S, Bland-Ward PA, Moore PK, Jenner P, Marsden CD. Time course of inhibition of brain nitric oxide synthase by 7-nitro indazole. Neuroreport. 1994;5(15):1993-1996. doi:10.1097/00001756-199410000-00039
• Moore PK, Babbedge RC, Wallace P, Gaffen, ZA, Hart SL. 7‐Nitro indazole, an inhibitor of nitric oxide synthase, exhibits anti‐nociceptive activity in the mouse without increasing blood pressure. British journal of pharmacology. 1993;108(2):296-297. doi:10.1111/j.1476-5381.1993.tb12798.x
• Starr MS, Starr BS. Paradoxical facilitation of pilocarpine-induced seizures in the mouse by MK-801 and the nitric oxide synthesis inhibitor L-NAME. Pharmacology Biochemistry and Behavior. 1993;45(2):321-325. doi:10.1016/0091-3057(93)90246-P
• Stringer JL, Erden F. In the hippocampus in vivo, nitric oxide does not appear to function as an endogenous antiepileptic agent. Experimental brain research. 1990;105(3):391-401.
• Penix LP, Davis W, Subramaniam S. Inhibition of NO synthase increases the severity of kainic acid-induced seizures in rodents. Epilepsy research. 1994;18(3):177-184. doi:10.1016/0920-1211(94)90038-8
• De Sarro GB, Di Paola ED, De Sarro A, Vidal MJ. Role of nitric oxide in the genesis of excitatory amino acid‐induced seizures from the deep prepiriform cortex. Fundamental & clinical pharmacology. 1991;5(6):503-511. doi:10.1111/j.1472-8206.1991.tb00737.x
• De Sarro G, Di Paola ED, De Sarro A, Vidal MJ. L-Arginine potentiates excitatory amino acid-induced seizures elicited in the deep prepiriform cortex. European journal of pharmacology. 1993;230(2):151-158. doi:10.1016/0014-2999(93)90797-L
• Mollace V, BagettaG, Nistico G. Evidence that L-arginine possesses proconvulsant effects mediated through nitric oxide. Neuroreport. 1991;2(5):269-272. doi:10.1097/00001756-199105000-00014
• Osonoe K, Mori N, Suzuki K, Osonoe M. Antiepileptic effects of inhibitors of nitric oxide synthase examined in pentylenetetrazol-induced seizures in rats. Brain research. 1994; 663(2):338-340. doi:10.1016/0006-8993(94)91283-1
• Mülsch A, Busse R, Mordvintcev PI, et al. Nitric oxide promotes seizure activity in kainate-treated rats. Neuroreport. 1994;5(17):2325-2328.
• Hara S, Kuriiwa F, Iwata N, Mukai T, Kano S, Endo T. Distinct Effects of N arnitro-L-arginine on seizures induced by several drugs in mice. Pharmaco/ Biochem Behav. 1996;53 (3):673-677. doi:10.1016/0091-3057(95)02068-3
• Wang Q, Theard MA, Pelligrino DA, et al. Nitric oxide (NO) is an endogenous anticonvulsant but not a mediator of the increase in cerebral blood flow accompanying bicuculline-induced seizures in rats. Brain research. 1994;658(1-2):192-198. doi:10.1016/S0006-8993(09)90026-9