Abstract
Unilateral focal injection of 1,3-di(2-tolyl)guanidine (DTG) caused a dose-dependent and potent (ED50 = 5.25 nmol, 95% confidence limits 1.1 to 25.0 nmol) suppression of generalized motor seizures induced by (-)-bicuculline methiodide in the rat prepiriform cortex. These findings indicate that DTG is equipotent to the noncompetitive NMDA receptor antagonist MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate) as an anticonvulsant. This potent pharmacological effect of DTG distinguishes it from two other prototypic σ ligands, haloperidol and (+)-pentazocine, which are ineffective as anticonvulsants. Pretreatment of animals with haloperidol failed to block the anticonvulsant effects of DTG. These data therefore document a novel anticonvulsant action of DTG in vivo by a mechanism that does not involve σ receptors.
| Original language | English |
|---|---|
| Pages (from-to) | 327-331 |
| Number of pages | 5 |
| Journal | European Journal of Pharmacology |
| Volume | 236 |
| Issue number | 2 |
| DOIs | |
| State | Published - May 19 1993 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Cellular and Molecular Neuroscience
- Pharmacology
Cite this
The σ receptor ligand 1,3-di(2-tolyl)guanidine is anticonvulsant in the rat prepiriform cortex. / Roth, Jane E.; Franklin, Paul H.; Murray, Thomas F.
In: European Journal of Pharmacology, Vol. 236, No. 2, 19.05.1993, p. 327-331.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The σ receptor ligand 1,3-di(2-tolyl)guanidine is anticonvulsant in the rat prepiriform cortex
AU - Roth, Jane E.
AU - Franklin, Paul H.
AU - Murray, Thomas F.
PY - 1993/5/19
Y1 - 1993/5/19
N2 - Unilateral focal injection of 1,3-di(2-tolyl)guanidine (DTG) caused a dose-dependent and potent (ED50 = 5.25 nmol, 95% confidence limits 1.1 to 25.0 nmol) suppression of generalized motor seizures induced by (-)-bicuculline methiodide in the rat prepiriform cortex. These findings indicate that DTG is equipotent to the noncompetitive NMDA receptor antagonist MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate) as an anticonvulsant. This potent pharmacological effect of DTG distinguishes it from two other prototypic σ ligands, haloperidol and (+)-pentazocine, which are ineffective as anticonvulsants. Pretreatment of animals with haloperidol failed to block the anticonvulsant effects of DTG. These data therefore document a novel anticonvulsant action of DTG in vivo by a mechanism that does not involve σ receptors.
AB - Unilateral focal injection of 1,3-di(2-tolyl)guanidine (DTG) caused a dose-dependent and potent (ED50 = 5.25 nmol, 95% confidence limits 1.1 to 25.0 nmol) suppression of generalized motor seizures induced by (-)-bicuculline methiodide in the rat prepiriform cortex. These findings indicate that DTG is equipotent to the noncompetitive NMDA receptor antagonist MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate) as an anticonvulsant. This potent pharmacological effect of DTG distinguishes it from two other prototypic σ ligands, haloperidol and (+)-pentazocine, which are ineffective as anticonvulsants. Pretreatment of animals with haloperidol failed to block the anticonvulsant effects of DTG. These data therefore document a novel anticonvulsant action of DTG in vivo by a mechanism that does not involve σ receptors.
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U2 - 10.1016/0014-2999(93)90607-J
DO - 10.1016/0014-2999(93)90607-J
M3 - Article
VL - 236
SP - 327
EP - 331
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 2
ER -