European Neuropsychopharmacology, 2 (1992) 157-159 ~; 1992 Elsevier Science Publishers B.V. All rights reserved 0924-977X/92/$05.00
157
ENP 00052
Short Communication
Sigma receptor modulation of the muscle relaxant action of eperisone Yutaka Hasegawa, Shinsuke Kaku, Hiroaki Araki and Susumu Otomo Department ~?]Pharmacology, Research Center, Taisho Pharmaceutical Co., Ltd., 403 Yoshino-cho 1-chome, Ohmiya, Saitama 330, Japan (Received 31 July, 1991) (Revised, received 6 January, 1992) (Accepted 22 January, 1992)
Key words." a-Receptors; Straub tail; Eperisone Summary
We examined the mechanism of the muscle relaxant action of eperisone, using Straub tail and binding studies. In vivo, eperisone (50 and 100 mg/kg i.p.) produced a dose-dependent inhibition of the Straub tail in mice and this inhibitory effect was significantly reversed by haloperidol (0.5 mg/kg i.p.). This drug in itself had no effect on the Straub tail. Sulpiride (50 mg/kg i.p.) failed to reverse the inhibitory effect of eperisone. In vitro, (+)-3-(3-[3H]hydroxyphenyl)-N-(1-propylpiperidine) ((+)-[3H]3-PPP) specific binding, in rat brain membrane, was prevented by eperisone and the ICs0 value was 0.43 nM. The muscle relaxant action of eperisone may be modulated by a receptors.
Introduction
Eperisone (4'-ethyl-2-methyl-3-piperidinopropiophenone hydrochloride) inhibits monosynaptic and polysynaptic reflexes and acts as a central muscle relaxant (Tanaka et al., 1981). The specific binding site of eperisone has remained unknown. The Straub tail is a useful model for screening central muscle relaxants (Srimal et al., 1965) and for examining neuronal receptors involved in spinal cord excitation (Hasegawa et al., 1990a,b). a receptors were identified by Martin et al. (1976), based on the action of (+)-N-allylnormetazocine (SKF 10,047) and related benzomorphan alkaloids. Walker et al. (1988) considered Correspondence to: Y. Hasegawa, Department of Pharmacology, Research Center, Taisho Pharmaceutical Co., Ltd., 403 Yoshino-cho 1-chome, Ohmiya, Saitama 330, Japan. Tel.: 048-663-1111; Fax: 048-652-7254.
that a receptors were biologically functional with regard to effects on motor events. In the present study, we attempted to determine the relationship between the action of eperisone and a receptors, using high affinity ligands for a receptors, haloperidol and (+)-3-PPP, on the Straub tail test and binding studies.
Materials and methods
ICR male mice (Charles River, Japan), weighing 20-30 g, were used for the Straub tail test. Eperisone (100 mg/kg i.p.) was administered 15 min after morphine (10 mg/kg s.c.) and tail elevation was measured 30 min after morphine administration, according to the method of Hasegawa et al. (1990a) as follows: 0 = 0 °, 1 = 1 30 °,2 = 31-60 °,3 = 61-90 °,4 = >90 °,above from the horizontal table plane. Haloperidol
158 (Serenace:":; Dainippon, Japan) or sulpiride (Dogmatyl
157
ENP 00052
Short Communication
Sigma receptor modulation of the muscle relaxant action of eperisone Yutaka Hasegawa, Shinsuke Kaku, Hiroaki Araki and Susumu Otomo Department ~?]Pharmacology, Research Center, Taisho Pharmaceutical Co., Ltd., 403 Yoshino-cho 1-chome, Ohmiya, Saitama 330, Japan (Received 31 July, 1991) (Revised, received 6 January, 1992) (Accepted 22 January, 1992)
Key words." a-Receptors; Straub tail; Eperisone Summary
We examined the mechanism of the muscle relaxant action of eperisone, using Straub tail and binding studies. In vivo, eperisone (50 and 100 mg/kg i.p.) produced a dose-dependent inhibition of the Straub tail in mice and this inhibitory effect was significantly reversed by haloperidol (0.5 mg/kg i.p.). This drug in itself had no effect on the Straub tail. Sulpiride (50 mg/kg i.p.) failed to reverse the inhibitory effect of eperisone. In vitro, (+)-3-(3-[3H]hydroxyphenyl)-N-(1-propylpiperidine) ((+)-[3H]3-PPP) specific binding, in rat brain membrane, was prevented by eperisone and the ICs0 value was 0.43 nM. The muscle relaxant action of eperisone may be modulated by a receptors.
Introduction
Eperisone (4'-ethyl-2-methyl-3-piperidinopropiophenone hydrochloride) inhibits monosynaptic and polysynaptic reflexes and acts as a central muscle relaxant (Tanaka et al., 1981). The specific binding site of eperisone has remained unknown. The Straub tail is a useful model for screening central muscle relaxants (Srimal et al., 1965) and for examining neuronal receptors involved in spinal cord excitation (Hasegawa et al., 1990a,b). a receptors were identified by Martin et al. (1976), based on the action of (+)-N-allylnormetazocine (SKF 10,047) and related benzomorphan alkaloids. Walker et al. (1988) considered Correspondence to: Y. Hasegawa, Department of Pharmacology, Research Center, Taisho Pharmaceutical Co., Ltd., 403 Yoshino-cho 1-chome, Ohmiya, Saitama 330, Japan. Tel.: 048-663-1111; Fax: 048-652-7254.
that a receptors were biologically functional with regard to effects on motor events. In the present study, we attempted to determine the relationship between the action of eperisone and a receptors, using high affinity ligands for a receptors, haloperidol and (+)-3-PPP, on the Straub tail test and binding studies.
Materials and methods
ICR male mice (Charles River, Japan), weighing 20-30 g, were used for the Straub tail test. Eperisone (100 mg/kg i.p.) was administered 15 min after morphine (10 mg/kg s.c.) and tail elevation was measured 30 min after morphine administration, according to the method of Hasegawa et al. (1990a) as follows: 0 = 0 °, 1 = 1 30 °,2 = 31-60 °,3 = 61-90 °,4 = >90 °,above from the horizontal table plane. Haloperidol
158 (Serenace:":; Dainippon, Japan) or sulpiride (Dogmatyl
