[Effects of terguride, an ergot alkaloid derivative, on the central nervous system: biochemical and behavioral studies].
Effects of terguride, a 9,10-dihydrogenated derivative of lisuride, on the central nervous system were investigated in rodents in comparison with those of lisuride. In vitro binding studies in rat brains showed that terguride, similar to lisuride, had a high affinity for D2-, 5-HT1A-, 5-HT2-, alpha 1- and alpha 2-receptors. Terguride, as does lisuride, induced hypomotility and yawning at low doses in rats, suggesting its presynaptic D2-agonist action. Terguride, unlike the postsynaptic D2-agonist lisuride, induced neither hypermotility nor stereotypy in rats and guinea pigs, but suppressed the hypermotility and stereotypy induced by apomorphine. Terguride suppressed haloperidol-induced catalepsy in rats and induced contralateral rotations in unilaterally 6-OHDA-lesioned rats, as does lisuride. These effects may be due to the postsynaptic D2 partial agonist action. Terguride, unlike lisuride, neither induced the serotonin syndrome nor generalized to the discriminative stimuli of the 5-HT1A- agonist 8-OH-DPAT in rats. Terguride did not induce head twitch in mice. Terguride blocked noradrenaline-induced lethality and clonidine-induced hypothermia at high doses in mice. Repeated administration of terguride did not affect the behavioral actions in rats. Thus, the effects of terguride on the central nervous system seems to be produced by mediation of the agonist and partial agonist actions at presynaptic and postsynaptic D2- receptors, respectively.
Ikoma
Y
Y
Research Department, Nihon Schering K.K., Osaka, Japan.
Akai
T
T
Nakata
Y
Y
Hara
K
K
Wachtel
H
H
Yamaguchi
M
M
D000818:Animals; D002375:Catalepsy / Q000139:chemically induced; D004876:Ergot Alkaloids / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D008090:Lisuride / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects*; D015000:Yawning / Q000187:drug effects
D004876:Ergot Alkaloids; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; C006208:dironyl; D008090:Lisuride