Anticonvulsant activity of PNU-151774E in the amygdala kindled model of complex partial seizures

Roberto Maj, Ruggero G. Fariello, Paolo Pevarello, Mario Varasi, Robert A. McArthur, Patricia Salvati

Research output: Contribution to journalArticle

Abstract

Purpose: PNU-151774E [(S)-(+)-2-(4-(3-fluorobenzyloxy) benzylamino) propanamide, methanesulfonate] is a novel antiepileptic drag (AED) with a broad spectrum of activity in a variety of chemically and mechanically induced seizures. The objective of this study was to evaluate the activity of PNU-151774E in the amygdala fully kindled rat model of complex partial seizures, and to compare its effects with those of carbamazepine (CBZ), phenytoin (PHT), lamotrigine (LTG), and gabapentin (GBP), drugs used to treat this disease state. Methods: Male Wistar rats were stimulated daily through electrodes implanted in the amygdala with a threshold current until fully generalized seizures developed. The rats were then treated with various doses of a single compound. Control values for each rat and drug dose were determined after vehicle administration followed by electrical stimulation I day before drag treatment. Results: PNU-151774E (1, 10, 30 mg/kg; i.p.) reduced the duration of behavioral seizures significantly and dose- dependently at doses starting from 1 mg/kg. Higher doses significantly reduced seizure severity and afterdischarge duration. In contrast, no dose- related effects were noted after administration of PHT, whereas after CBZ treatment, a plateau of activity was noted from the intermediate to higher doses. The effects of PNU-151774E were comparable to those of LTG and GBP. Conclusions: The activity shown by PNU-151774E at doses similar to those that are active in models of generalized seizures indicates that PNU-151774E would also have potential efficacy in the treatment of complex partial seizures.

Original languageEnglish
Pages (from-to)1523-1528
Number of pages6
JournalEpilepsia
Volume40
Issue number11
DOIs
Publication statusPublished - 1999

Fingerprint

Amygdala
Anticonvulsants
Seizures
Carbamazepine
Phenytoin
Implanted Electrodes
safinamide
Pharmaceutical Preparations
Electric Stimulation
Wistar Rats

Keywords

  • Carbamazepine
  • Complex partial seizures
  • Gabapentine
  • Kindling
  • Lamotrigine
  • Phenytoin
  • PNU-151774E
  • Rat

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Maj, R., Fariello, R. G., Pevarello, P., Varasi, M., McArthur, R. A., & Salvati, P. (1999). Anticonvulsant activity of PNU-151774E in the amygdala kindled model of complex partial seizures. Epilepsia, 40(11), 1523-1528. https://doi.org/10.1111/j.1528-1157.1999.tb02035.x

Anticonvulsant activity of PNU-151774E in the amygdala kindled model of complex partial seizures. / Maj, Roberto; Fariello, Ruggero G.; Pevarello, Paolo; Varasi, Mario; McArthur, Robert A.; Salvati, Patricia.

In: Epilepsia, Vol. 40, No. 11, 1999, p. 1523-1528.

Research output: Contribution to journalArticle

Maj, R, Fariello, RG, Pevarello, P, Varasi, M, McArthur, RA & Salvati, P 1999, 'Anticonvulsant activity of PNU-151774E in the amygdala kindled model of complex partial seizures', Epilepsia, vol. 40, no. 11, pp. 1523-1528. https://doi.org/10.1111/j.1528-1157.1999.tb02035.x
Maj, Roberto ; Fariello, Ruggero G. ; Pevarello, Paolo ; Varasi, Mario ; McArthur, Robert A. ; Salvati, Patricia. / Anticonvulsant activity of PNU-151774E in the amygdala kindled model of complex partial seizures. In: Epilepsia. 1999 ; Vol. 40, No. 11. pp. 1523-1528.
@article{6ad46b2d86bf4a0999bd378badca99aa,
title = "Anticonvulsant activity of PNU-151774E in the amygdala kindled model of complex partial seizures",
abstract = "Purpose: PNU-151774E [(S)-(+)-2-(4-(3-fluorobenzyloxy) benzylamino) propanamide, methanesulfonate] is a novel antiepileptic drag (AED) with a broad spectrum of activity in a variety of chemically and mechanically induced seizures. The objective of this study was to evaluate the activity of PNU-151774E in the amygdala fully kindled rat model of complex partial seizures, and to compare its effects with those of carbamazepine (CBZ), phenytoin (PHT), lamotrigine (LTG), and gabapentin (GBP), drugs used to treat this disease state. Methods: Male Wistar rats were stimulated daily through electrodes implanted in the amygdala with a threshold current until fully generalized seizures developed. The rats were then treated with various doses of a single compound. Control values for each rat and drug dose were determined after vehicle administration followed by electrical stimulation I day before drag treatment. Results: PNU-151774E (1, 10, 30 mg/kg; i.p.) reduced the duration of behavioral seizures significantly and dose- dependently at doses starting from 1 mg/kg. Higher doses significantly reduced seizure severity and afterdischarge duration. In contrast, no dose- related effects were noted after administration of PHT, whereas after CBZ treatment, a plateau of activity was noted from the intermediate to higher doses. The effects of PNU-151774E were comparable to those of LTG and GBP. Conclusions: The activity shown by PNU-151774E at doses similar to those that are active in models of generalized seizures indicates that PNU-151774E would also have potential efficacy in the treatment of complex partial seizures.",
keywords = "Carbamazepine, Complex partial seizures, Gabapentine, Kindling, Lamotrigine, Phenytoin, PNU-151774E, Rat",
author = "Roberto Maj and Fariello, {Ruggero G.} and Paolo Pevarello and Mario Varasi and McArthur, {Robert A.} and Patricia Salvati",
year = "1999",
doi = "10.1111/j.1528-1157.1999.tb02035.x",
language = "English",
volume = "40",
pages = "1523--1528",
journal = "Epilepsia",
issn = "0013-9580",
publisher = "Blackwell Publishing Inc.",
number = "11",

}

TY - JOUR

T1 - Anticonvulsant activity of PNU-151774E in the amygdala kindled model of complex partial seizures

AU - Maj, Roberto

AU - Fariello, Ruggero G.

AU - Pevarello, Paolo

AU - Varasi, Mario

AU - McArthur, Robert A.

AU - Salvati, Patricia

PY - 1999

Y1 - 1999

N2 - Purpose: PNU-151774E [(S)-(+)-2-(4-(3-fluorobenzyloxy) benzylamino) propanamide, methanesulfonate] is a novel antiepileptic drag (AED) with a broad spectrum of activity in a variety of chemically and mechanically induced seizures. The objective of this study was to evaluate the activity of PNU-151774E in the amygdala fully kindled rat model of complex partial seizures, and to compare its effects with those of carbamazepine (CBZ), phenytoin (PHT), lamotrigine (LTG), and gabapentin (GBP), drugs used to treat this disease state. Methods: Male Wistar rats were stimulated daily through electrodes implanted in the amygdala with a threshold current until fully generalized seizures developed. The rats were then treated with various doses of a single compound. Control values for each rat and drug dose were determined after vehicle administration followed by electrical stimulation I day before drag treatment. Results: PNU-151774E (1, 10, 30 mg/kg; i.p.) reduced the duration of behavioral seizures significantly and dose- dependently at doses starting from 1 mg/kg. Higher doses significantly reduced seizure severity and afterdischarge duration. In contrast, no dose- related effects were noted after administration of PHT, whereas after CBZ treatment, a plateau of activity was noted from the intermediate to higher doses. The effects of PNU-151774E were comparable to those of LTG and GBP. Conclusions: The activity shown by PNU-151774E at doses similar to those that are active in models of generalized seizures indicates that PNU-151774E would also have potential efficacy in the treatment of complex partial seizures.

AB - Purpose: PNU-151774E [(S)-(+)-2-(4-(3-fluorobenzyloxy) benzylamino) propanamide, methanesulfonate] is a novel antiepileptic drag (AED) with a broad spectrum of activity in a variety of chemically and mechanically induced seizures. The objective of this study was to evaluate the activity of PNU-151774E in the amygdala fully kindled rat model of complex partial seizures, and to compare its effects with those of carbamazepine (CBZ), phenytoin (PHT), lamotrigine (LTG), and gabapentin (GBP), drugs used to treat this disease state. Methods: Male Wistar rats were stimulated daily through electrodes implanted in the amygdala with a threshold current until fully generalized seizures developed. The rats were then treated with various doses of a single compound. Control values for each rat and drug dose were determined after vehicle administration followed by electrical stimulation I day before drag treatment. Results: PNU-151774E (1, 10, 30 mg/kg; i.p.) reduced the duration of behavioral seizures significantly and dose- dependently at doses starting from 1 mg/kg. Higher doses significantly reduced seizure severity and afterdischarge duration. In contrast, no dose- related effects were noted after administration of PHT, whereas after CBZ treatment, a plateau of activity was noted from the intermediate to higher doses. The effects of PNU-151774E were comparable to those of LTG and GBP. Conclusions: The activity shown by PNU-151774E at doses similar to those that are active in models of generalized seizures indicates that PNU-151774E would also have potential efficacy in the treatment of complex partial seizures.

KW - Carbamazepine

KW - Complex partial seizures

KW - Gabapentine

KW - Kindling

KW - Lamotrigine

KW - Phenytoin

KW - PNU-151774E

KW - Rat

UR - http://www.scopus.com/inward/record.url?scp=0342712672&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0342712672&partnerID=8YFLogxK

U2 - 10.1111/j.1528-1157.1999.tb02035.x

DO - 10.1111/j.1528-1157.1999.tb02035.x

M3 - Article

C2 - 10565578

AN - SCOPUS:0342712672

VL - 40

SP - 1523

EP - 1528

JO - Epilepsia

JF - Epilepsia

SN - 0013-9580

IS - 11

ER -