Electroencephalographic study on sedative effect of talipexole, a novel antiparkinsonian drug, in rats with chronic electrode implants

Yasuko Kohno, Shigenobu Shibata, Masuo Ohno, Shigenori Watanabe

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Talipexole (B-HT 920 CL2) is expected to be a novel antiparkinsonian drug with higher efficacy and lesser gastrointestinal side effects as compared with conventional dopamine receptor agonists. On the other hand, because of D2 and α2-autoreceptor stimulation by talipexole, it produces more marked sedative effects in clinical trial and animal behavioral studies. In the present experiments, electroencephalographic (EEG) effects of talipexole were investigated in unanesthetized rats with chronic electrode implants. The changes in the spontaneous EEG were evaluated during dark time with rats which had been housed in a room maintained on a reversed light dark cycle (lights on from 19 : 00 to 7 : 00) for 7 days. Talipexole at 10 μg/kg, s.c. induced a slight drowsy pattern: high voltage slow waves in the frontal cortex and disappearance of hippocampal theta rhythm. At doses of 32 and 100 μg/kg, s.c., talipexole caused a more marked drowsy pattern in the spontaneous EEG and significant decreases in the sedative score assessed by simultaneous observations of the EEG and behavioral motor activities. On the other hand, bromocriptine at 1 and 10 mg/kg, s.c. caused only a slight and temporal drowsy pattern in the spontaneous EEG without changing the arousal score. Then, the EEG arousal response induced by electrical stimulation of the mesencephalic reticular formation was studied during light time in rats which had been housed in a room maintained on a normal light dark cycle (lights on from 7 : 00 to 19 : 00). Both talipexole and bromocriptine slightly increased the threshold voltage to induce arousal response; however, the drug induced changes were not dose dependent. These results indicate that talipexole exhibits a sedative effect at much lower doses than bromocriptine, and that its sedative effect seems to he relatively weak and quite different from those noted with sleep inducers

Original languageEnglish
Pages (from-to)45-52
Number of pages8
JournalPharmacometrics
Volume51
Issue number2
Publication statusPublished - 1996 Feb
Externally publishedYes

Fingerprint

Antiparkinson Agents
Hypnotics and Sedatives
Electrodes
Pharmaceutical Preparations
Bromocriptine
Arousal
Photoperiod
Theta Rhythm
Light
Autoreceptors
talipexole
Dopamine Agonists
Frontal Lobe
Electric Stimulation
Motor Activity
Clinical Trials

Keywords

  • (rat)
  • Antiparkinsonian drug
  • EEG
  • Talipexole

ASJC Scopus subject areas

  • Pharmacology

Cite this

Electroencephalographic study on sedative effect of talipexole, a novel antiparkinsonian drug, in rats with chronic electrode implants. / Kohno, Yasuko; Shibata, Shigenobu; Ohno, Masuo; Watanabe, Shigenori.

In: Pharmacometrics, Vol. 51, No. 2, 02.1996, p. 45-52.

Research output: Contribution to journalArticle

@article{f82aae52bc3045d7af0caedc69b103c3,
title = "Electroencephalographic study on sedative effect of talipexole, a novel antiparkinsonian drug, in rats with chronic electrode implants",
abstract = "Talipexole (B-HT 920 CL2) is expected to be a novel antiparkinsonian drug with higher efficacy and lesser gastrointestinal side effects as compared with conventional dopamine receptor agonists. On the other hand, because of D2 and α2-autoreceptor stimulation by talipexole, it produces more marked sedative effects in clinical trial and animal behavioral studies. In the present experiments, electroencephalographic (EEG) effects of talipexole were investigated in unanesthetized rats with chronic electrode implants. The changes in the spontaneous EEG were evaluated during dark time with rats which had been housed in a room maintained on a reversed light dark cycle (lights on from 19 : 00 to 7 : 00) for 7 days. Talipexole at 10 μg/kg, s.c. induced a slight drowsy pattern: high voltage slow waves in the frontal cortex and disappearance of hippocampal theta rhythm. At doses of 32 and 100 μg/kg, s.c., talipexole caused a more marked drowsy pattern in the spontaneous EEG and significant decreases in the sedative score assessed by simultaneous observations of the EEG and behavioral motor activities. On the other hand, bromocriptine at 1 and 10 mg/kg, s.c. caused only a slight and temporal drowsy pattern in the spontaneous EEG without changing the arousal score. Then, the EEG arousal response induced by electrical stimulation of the mesencephalic reticular formation was studied during light time in rats which had been housed in a room maintained on a normal light dark cycle (lights on from 7 : 00 to 19 : 00). Both talipexole and bromocriptine slightly increased the threshold voltage to induce arousal response; however, the drug induced changes were not dose dependent. These results indicate that talipexole exhibits a sedative effect at much lower doses than bromocriptine, and that its sedative effect seems to he relatively weak and quite different from those noted with sleep inducers",
keywords = "(rat), Antiparkinsonian drug, EEG, Talipexole",
author = "Yasuko Kohno and Shigenobu Shibata and Masuo Ohno and Shigenori Watanabe",
year = "1996",
month = "2",
language = "English",
volume = "51",
pages = "45--52",
journal = "Pharmacometrics",
issn = "0300-8533",
publisher = "Japanese Society of Pharmacometrics",
number = "2",

}

TY - JOUR

T1 - Electroencephalographic study on sedative effect of talipexole, a novel antiparkinsonian drug, in rats with chronic electrode implants

AU - Kohno, Yasuko

AU - Shibata, Shigenobu

AU - Ohno, Masuo

AU - Watanabe, Shigenori

PY - 1996/2

Y1 - 1996/2

N2 - Talipexole (B-HT 920 CL2) is expected to be a novel antiparkinsonian drug with higher efficacy and lesser gastrointestinal side effects as compared with conventional dopamine receptor agonists. On the other hand, because of D2 and α2-autoreceptor stimulation by talipexole, it produces more marked sedative effects in clinical trial and animal behavioral studies. In the present experiments, electroencephalographic (EEG) effects of talipexole were investigated in unanesthetized rats with chronic electrode implants. The changes in the spontaneous EEG were evaluated during dark time with rats which had been housed in a room maintained on a reversed light dark cycle (lights on from 19 : 00 to 7 : 00) for 7 days. Talipexole at 10 μg/kg, s.c. induced a slight drowsy pattern: high voltage slow waves in the frontal cortex and disappearance of hippocampal theta rhythm. At doses of 32 and 100 μg/kg, s.c., talipexole caused a more marked drowsy pattern in the spontaneous EEG and significant decreases in the sedative score assessed by simultaneous observations of the EEG and behavioral motor activities. On the other hand, bromocriptine at 1 and 10 mg/kg, s.c. caused only a slight and temporal drowsy pattern in the spontaneous EEG without changing the arousal score. Then, the EEG arousal response induced by electrical stimulation of the mesencephalic reticular formation was studied during light time in rats which had been housed in a room maintained on a normal light dark cycle (lights on from 7 : 00 to 19 : 00). Both talipexole and bromocriptine slightly increased the threshold voltage to induce arousal response; however, the drug induced changes were not dose dependent. These results indicate that talipexole exhibits a sedative effect at much lower doses than bromocriptine, and that its sedative effect seems to he relatively weak and quite different from those noted with sleep inducers

AB - Talipexole (B-HT 920 CL2) is expected to be a novel antiparkinsonian drug with higher efficacy and lesser gastrointestinal side effects as compared with conventional dopamine receptor agonists. On the other hand, because of D2 and α2-autoreceptor stimulation by talipexole, it produces more marked sedative effects in clinical trial and animal behavioral studies. In the present experiments, electroencephalographic (EEG) effects of talipexole were investigated in unanesthetized rats with chronic electrode implants. The changes in the spontaneous EEG were evaluated during dark time with rats which had been housed in a room maintained on a reversed light dark cycle (lights on from 19 : 00 to 7 : 00) for 7 days. Talipexole at 10 μg/kg, s.c. induced a slight drowsy pattern: high voltage slow waves in the frontal cortex and disappearance of hippocampal theta rhythm. At doses of 32 and 100 μg/kg, s.c., talipexole caused a more marked drowsy pattern in the spontaneous EEG and significant decreases in the sedative score assessed by simultaneous observations of the EEG and behavioral motor activities. On the other hand, bromocriptine at 1 and 10 mg/kg, s.c. caused only a slight and temporal drowsy pattern in the spontaneous EEG without changing the arousal score. Then, the EEG arousal response induced by electrical stimulation of the mesencephalic reticular formation was studied during light time in rats which had been housed in a room maintained on a normal light dark cycle (lights on from 7 : 00 to 19 : 00). Both talipexole and bromocriptine slightly increased the threshold voltage to induce arousal response; however, the drug induced changes were not dose dependent. These results indicate that talipexole exhibits a sedative effect at much lower doses than bromocriptine, and that its sedative effect seems to he relatively weak and quite different from those noted with sleep inducers

KW - (rat)

KW - Antiparkinsonian drug

KW - EEG

KW - Talipexole

UR - http://www.scopus.com/inward/record.url?scp=0029990191&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029990191&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:0029990191

VL - 51

SP - 45

EP - 52

JO - Pharmacometrics

JF - Pharmacometrics

SN - 0300-8533

IS - 2

ER -