Role of nitric oxide in the anticonvulsive effect of progesterone.
Described here is an investigation of the potential interaction of the nitric oxide signaling pathway with the anticonvulsant effects of progesterone. In ovariectomized Swiss mice, the threshold for seizures induced by intravenous infusion of pentylenetetrazole was determined after treatment with progesterone (25, 50, or 75 mg/kg, given subcutaneously 6h before seizure testing) or vehicle. Progesterone induced significant anticonvulsive activity at moderate (50 mg/kg) and high (75 mg/kg) doses. This effect of progesterone was abolished by the NO precursor compound L-arginine (200 mg/kg). Moreover, when subeffective doses of progesterone (25 mg/kg) and the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (10 mg/kg) were injected, a strong anticonvulsant effect was observed. These findings suggest a potential role for NO signaling as an anticonvulsant target in females.
Gholipour
Taha
T
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Jabbarzadeh
Atieh
A
Riazi
Kiarash
K
Rasouli
Aylar
A
Nezami
Behtash Ghazi
BG
Sharifzadeh
Mohammad
M
Dehpour
Ahmad Reza
AR
D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001120:Arginine / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010052:Ovariectomy; D010433:Pentylenetetrazole; D011374:Progesterone / Q000627:therapeutic use*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013997:Time Factors
D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D011374:Progesterone; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester; D010433:Pentylenetetrazole