We have studied the effects of selective and non-selective adenosine receptor agonists and antagonists in audiopenic-seizure-sensitive DBA/2 mice, an animal model of generalized reflex epilepsy. With the exception of the adenosine A(3) receptor agonist, N-6-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine (IB-MECA), all the agonists studied prevented the development of audiogenic seizures in a dose-dependent manner. The ED50 values against the clonic phase of the audiogenic seizures were low, that is: 0.06 mg/kg, i.p., for the adenosine A(1) receptor agonist, 2-chloro-N-6-cyclopentyladenosine (CCPA), 0.02 and 0.03 mg/kg, i.p., for the adenosine A(2A) receptor agonists, 2-(4-(2-carboxyethyl)-phenylamino)-5'-N-ethylcarboxamidoadenosine (CGS 21680) and 2-hexynyl-5'-N-ethyl-carboxamidoadenosine (2-HE-NECA), and 0.7 mg/kg, i.p., for the adenosine A(1)/A(3) receptor agonist, N-6-2-(4-aminophenyl)ethyladenosine (APNEA). Conversely, the non-selective agonist, N-ethyl-carboxamidoadenosine (NECA), was highly potent, the ED50 being 0.0005 mg/kg, i.p. In the absence of auditory stimulation, the adenosine receptor antagonists increased the incidence of both clonic and tonic seizures in DBA/2 mice. The ED50 values were: for caffeine, 207.5 mg/kg, i.p., for the adenosine A(1) receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), 327.8 mg/kg i.p., for the adenosine A(2A) receptor antagonists, 3,7-dimethyl-1-propylxanthine (DPMX), 86.7 mg/kg i.p., for the (E,18%-Z,82%)7-methyl-8-(3,4-dimethoxystyryl)-1,3-dipropylxanthine (KF 17837), 69.1 mg/kg i.p., and 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo-(4,3-c)1,2,4-triaxzolo(1,5-c)-pyrimidine (SCH 58261), 321.8 mg/kg i.p. The rank order of convulsant potency in our epileptic model, following intracerebroventricular administration, was DPCPX > DMPX > 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (CSC)> KF 17837 > Caffeine > SCH 58261 > 5-amino-9-chloro-2-(2-furyl)-1,2,4-triazolo(1,5-c)quinazoline (CGS 15943). Following a subconvulsant audiogenic stimulus of 83 dB, all adenosine receptor antagonists induced both tonic and clonic seizures. The ED50 values for such proconvulsant effects were: for caffeine 0.04 mg/kg, i.p., for the adenosine A(1) receptor antagonist, DPCPX, 5.84 mg/kg, i.p., for the adenosine A(2A) receptor antagonists, DMPX, 0.02 mg/kg, i.p., CGS 15943, 0.29 mg/kg i.p., KF 17837, 0.57 mg/kg, i.p., CSC 0.12 mg/kg, i.p. and SCH 58261 0.07 mg/kg, i.p., respectively. These data suggest that stimulation of adenosine A(1) and A(2A) receptors is involved in the suppression of seizures. (C) 1999 Elsevier Science B.V. All rights reserved.
Effects of adenosine receptor agonists and antagonists on audiogenic seizure-sensible DBA/2 mice
De Sarro G;Donato Di Paola E
1999-01-01
Abstract
We have studied the effects of selective and non-selective adenosine receptor agonists and antagonists in audiopenic-seizure-sensitive DBA/2 mice, an animal model of generalized reflex epilepsy. With the exception of the adenosine A(3) receptor agonist, N-6-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine (IB-MECA), all the agonists studied prevented the development of audiogenic seizures in a dose-dependent manner. The ED50 values against the clonic phase of the audiogenic seizures were low, that is: 0.06 mg/kg, i.p., for the adenosine A(1) receptor agonist, 2-chloro-N-6-cyclopentyladenosine (CCPA), 0.02 and 0.03 mg/kg, i.p., for the adenosine A(2A) receptor agonists, 2-(4-(2-carboxyethyl)-phenylamino)-5'-N-ethylcarboxamidoadenosine (CGS 21680) and 2-hexynyl-5'-N-ethyl-carboxamidoadenosine (2-HE-NECA), and 0.7 mg/kg, i.p., for the adenosine A(1)/A(3) receptor agonist, N-6-2-(4-aminophenyl)ethyladenosine (APNEA). Conversely, the non-selective agonist, N-ethyl-carboxamidoadenosine (NECA), was highly potent, the ED50 being 0.0005 mg/kg, i.p. In the absence of auditory stimulation, the adenosine receptor antagonists increased the incidence of both clonic and tonic seizures in DBA/2 mice. The ED50 values were: for caffeine, 207.5 mg/kg, i.p., for the adenosine A(1) receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), 327.8 mg/kg i.p., for the adenosine A(2A) receptor antagonists, 3,7-dimethyl-1-propylxanthine (DPMX), 86.7 mg/kg i.p., for the (E,18%-Z,82%)7-methyl-8-(3,4-dimethoxystyryl)-1,3-dipropylxanthine (KF 17837), 69.1 mg/kg i.p., and 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo-(4,3-c)1,2,4-triaxzolo(1,5-c)-pyrimidine (SCH 58261), 321.8 mg/kg i.p. The rank order of convulsant potency in our epileptic model, following intracerebroventricular administration, was DPCPX > DMPX > 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (CSC)> KF 17837 > Caffeine > SCH 58261 > 5-amino-9-chloro-2-(2-furyl)-1,2,4-triazolo(1,5-c)quinazoline (CGS 15943). Following a subconvulsant audiogenic stimulus of 83 dB, all adenosine receptor antagonists induced both tonic and clonic seizures. The ED50 values for such proconvulsant effects were: for caffeine 0.04 mg/kg, i.p., for the adenosine A(1) receptor antagonist, DPCPX, 5.84 mg/kg, i.p., for the adenosine A(2A) receptor antagonists, DMPX, 0.02 mg/kg, i.p., CGS 15943, 0.29 mg/kg i.p., KF 17837, 0.57 mg/kg, i.p., CSC 0.12 mg/kg, i.p. and SCH 58261 0.07 mg/kg, i.p., respectively. These data suggest that stimulation of adenosine A(1) and A(2A) receptors is involved in the suppression of seizures. (C) 1999 Elsevier Science B.V. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
