Abstract:
:Following intraperitoneal administration, the selective cAMP phosphodiesterase (PDE) inhibitors rolipram, ICI 63 197 and Ro 20-1724 were investigated in mice in comparison with imipramine for their effectiveness in two classical test models for prediction of clinical antidepressant activity: antagonism of reserpine-induced hypothermia or hypokinesia and potentiation of yohimbine lethality. Rolipram was approximately 15 times more potent than imipramine or Ro 20-1724 and approximately as potent as ICI 63 197 in antagonizing reserpine-induced hypothermia. The antihypothermic effect of the phosphodiesterase inhibitors occurred at a smaller dose than that of imipramine. In contrast to imipramine, the phosphodiesterase inhibitors reversed reserpine-induced hypokinesia. Rolipram was approximately as potent as ICI 63 197 and about 15 times more potent than Ro 20-1724. Rolipram was approx. 5 times more potent than Ro 20-1724 and approx. as potent as imipramine or ICI 63 197 in potentiating the lethality of yohimbine. In both test models the (-)-isomer of rolipram was approx. 10-15 times more potent than the (+)-isomer, indicating a stereospecific mechanism of action. The present data suggest an antidepressant action of selective cAMP phosphodiesterase inhibitors due to enhancement of central noradrenergic transmission. The hypothesis is put forward that the increase of noradrenaline turnover induced by phosphodiesterase inhibitors in conjunction with the inhibitory action of the compounds on cAMP metabolism enables more efficient adaptative changes to occur at central synapses resulting in a rapid onset of the antidepressant activity. Preliminary results with rolipram in patients with endogenous depression seem to support this assumption.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Wachtel Hdoi
10.1016/0028-3908(83)90239-3subject
Has Abstractpub_date
1983-03-01 00:00:00pages
267-72issue
3eissn
0028-3908issn
1873-7064journal_volume
22pub_type
杂志文章abstract::Clinical evidence indicates brain serotonin (5-HT) stores and neurotransmission may be inadequate in subpopulations of individuals with autism, and this may contribute to characteristically impaired social behaviors. Findings that depletion of the 5-HT precursor tryptophan (TRP) worsens autism symptoms support this hy...
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journal_title:Neuropharmacology
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journal_title:Neuropharmacology
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pub_type: 杂志文章
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