Mivazerol is a new and selective alpha 2-adrenoceptor agonist which has demonstrated anti-ischemic effects, both in animals and in patients with
myocardial ischemia. In the present study,
mivazerol was evaluated for its ability to inhibit the release of
catecholamines and
serotonin (5-HT) in the hippocampus of freely moving rats, and also was compared to
clonidine. In vivo microdialysis in combination with high-performance liquid chromatography (HPLC) was employed.
Intravenous administration of
mivazerol (8.0 micrograms/kg) had no effect on basal outflow of
norepinephrine (NE),
dopamine (DA) and
3,4-dihydroxyphenylacetic acid (
DOPAC). In contrast,
clonidine (8.5 micrograms/kg, i.v.) attenuated the basal release of
DOPAC, which has been proposed to reflect NE biosynthesis, suggesting that
clonidine has an inhibitory effect on NE synthesis. In addition, both
mivazerol and
clonidine decreased the spontaneous release of
5-HT, which provided further evidence that alpha 2-adrenoceptors in the hippocampus modulate
5-HT. Sixty-min immobilization stress significantly increased the release of NE (177 +/- 28%), DA (209 +/- 46%) and
DOPAC (337 +/- 72%).
Mivazerol (2.5, 8.0 and 25 micrograms/kg, i.v.) completely prevented the immobilization stress-induced enhancement of NE, DA and
DOPAC, which was equi-effective to
clonidine at a dose of 8.5 micrograms/kg, i.v. These findings demonstrate that
mivazerol has a profound modulatory effect on stress-induced
neurotransmitter release in the hippocampus, at dose levels reported to protect against
myocardial ischemia.