TY - JOUR
T1 - Agmatine exerts anticonvulsant effect in mice
T2 - Modulation by α2-adrenoceptors and nitric oxide
AU - Demehri, Shadpour
AU - Homayoun, Houman
AU - Honar, Hooman
AU - Riazi, Kiarash
AU - Vafaie, Kourosh
AU - Roushanzamir, Farshad
AU - Dehpour, Ahmad Reza
PY - 2003/9
Y1 - 2003/9
N2 - The effect of agmatine, an endogenous polyamine metabolite, on seizure susceptibility was investigated in mice. Acute intraperitoneal administration of agmatine (5, 10, 20, 40 mg/kg) had a significant and dose-dependent inhibitory effect on pentylenetetrazole (PTZ)-induced seizures. The peak of this anticonvulsant effect was 45 min after agmatine administration. We further investigated the possible involvement of the α2-adrenoceptors and L-arginine/NO pathway in this effect of agmatine. The α2-adrenoceptor antagonist, yohimbine (0.5-2 mg/kg), induced a dose-dependent blockade of the anticonvulsant effect of agmatine. The nitric oxide synthase (NOS) substrate, L-arginine (60 mg/kg), inhibited the anticonvulsant property of agmatine and this effect was significantly reversed by NOS inhibitor NG-nitro-L-arginine (L-NAME, 30 mg/kg), implying an NO-dependent mechanism for L-arginine effect. We further examined a possible additive effect between agmatine (1 or 5 mg/kg) and L-NAME (10 mg/kg). The combination of L-NAME (10 mg/kg) with agmatine (5 but not 1 mg/kg) induced a significantly higher level of seizure protection as compared with each drug alone. Moreover, a combination of lower doses of yohimbine (0.5 mg/kg) and L-arginine (30 mg/kg) also significantly decreased the anticonvulsant effect of agmatine. In conclusion, the present data suggest that agmatine may be of potential use in seizure treatment.
AB - The effect of agmatine, an endogenous polyamine metabolite, on seizure susceptibility was investigated in mice. Acute intraperitoneal administration of agmatine (5, 10, 20, 40 mg/kg) had a significant and dose-dependent inhibitory effect on pentylenetetrazole (PTZ)-induced seizures. The peak of this anticonvulsant effect was 45 min after agmatine administration. We further investigated the possible involvement of the α2-adrenoceptors and L-arginine/NO pathway in this effect of agmatine. The α2-adrenoceptor antagonist, yohimbine (0.5-2 mg/kg), induced a dose-dependent blockade of the anticonvulsant effect of agmatine. The nitric oxide synthase (NOS) substrate, L-arginine (60 mg/kg), inhibited the anticonvulsant property of agmatine and this effect was significantly reversed by NOS inhibitor NG-nitro-L-arginine (L-NAME, 30 mg/kg), implying an NO-dependent mechanism for L-arginine effect. We further examined a possible additive effect between agmatine (1 or 5 mg/kg) and L-NAME (10 mg/kg). The combination of L-NAME (10 mg/kg) with agmatine (5 but not 1 mg/kg) induced a significantly higher level of seizure protection as compared with each drug alone. Moreover, a combination of lower doses of yohimbine (0.5 mg/kg) and L-arginine (30 mg/kg) also significantly decreased the anticonvulsant effect of agmatine. In conclusion, the present data suggest that agmatine may be of potential use in seizure treatment.
KW - Agmatine
KW - L-Arginine
KW - L-NAME
KW - Pentylenetetrazole
KW - Yohimbine
KW - α-Adrenergic
UR - http://www.scopus.com/inward/record.url?scp=0042698307&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0042698307&partnerID=8YFLogxK
U2 - 10.1016/S0028-3908(03)00199-0
DO - 10.1016/S0028-3908(03)00199-0
M3 - Article
C2 - 12907314
AN - SCOPUS:0042698307
SN - 0028-3908
VL - 45
SP - 534
EP - 542
JO - Neuropharmacology
JF - Neuropharmacology
IS - 4
ER -