Behavioral effects of rolipram and structurally related compounds in mice: Behavioral sedation of cAMP phosphodiesterase inhibitors
Pharmacology Biochemistry and BehaviorPublished 1 June 1991
Guy Griebel, René Misslin, Elise Vogel, Jean‐Jacques Bourguignon
Citations42
SJR quartileQ1
SJR score0.95
SNIP0.81
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
The results suggest that the increase of cAMP probably does not account for the previously observed anxiolytic properties of BW A78U, an adenine derivative PDE-I.
Abstract
The behavioral effects of specific cAMP phosphodiesterase inhibitors (PDE-I) such as rolipram and structurally related compounds were investigated in mice. Selected PDE-I induced a potent dose-dependent decrease in locomotion and in rearing of mice confronted with a free exploratory procedure, these effects being considered as a behavioral sedation. However, in the light/dark choice test especially conceived to reveal disinhibitory and/or anxiolytic action, they did not show obvious effects. These results suggest that the increase of cAMP probably does not account for our previously observed anxiolytic properties of BW A78U, an adenine derivative PDE-I (20).
Keywords
PsychologyNeuroscienceBiochemistry, Genetics and Molecular Biology
Pharmacology Biochemistry and BehaviorPreliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines
1,402 Citations1980Jacqueline N. Crawley, Frederick K. Goodwin
The increased exploratory activity with benzodiazepines does not appear to be a non-specific increase in general motor activity, as locomotion in clonazepam and chlordiazepoxide treated mice placed in a bare, undifferentiated cage was not significantly different from vehicle treated mice.
Trends in Pharmacological SciencesPrimary sequence of cyclic nucleotide phosphodiesterase isozymes and the design of selective inhibitors
850 Citations1990Joseph A. Beavo, David H. Reifsnyder
Much of the evidence that has led to the current understanding of multiple isozymes of phosphodiesterase is summarized, with emphasis on aspects that may be relevant to drug design.
NeuropharmacologyPotential antidepressant activity of rolipram and other selective cyclic adenosine 3′,5′-monophosphate phosphodiesterase inhibitors
243 Citations1983H. Wachtel
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.
European Journal of PharmacologyStereospecific binding of the antidepressant rolipram to brain protein structures
235 Citations1986Herbert H. Schneider, Ralph Schmiechen +2 more
The kinetics of (-)-[3H]rolipram binding to the particulate fraction revealed a complex association and dissociation behaviour, which may represent a rolipram-sensitive phosphodiesterase isoenzyme also common to some peripheral organs, while the high affinity binding site(s) may be related to PDE isoenzymes more confined to the central nervous system.
Molecular Pharmacology4-(3-Cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone (ZK 62711): a Potent Inhibitor of Adenosine Cyclic 3',5'-Monophosphate Phosphodiesterases in Homogenates and Tissue Slices from Rat Brain
219 Citations1976Ulrich Schwabe, M. Miyake +2 more
A new class of inhibitor of phosphodiesterases is represented by 4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone (ZK 62711), which enhances the magnitude of accumulations of cyclic 39,59-AMP elicited by norepinephrine, isoproterenol, histamine, and adenosine in rat cerebral cortical slices and by veratridine in mouse cerebellar slices.
Pharmacology Biochemistry and BehaviorAnxiogenic effects of methyl-β-carboline-3-carboxylate in a light/dark choice situation
164 Citations1987Catherine Belzung, René Misslin +3 more
The benzodiazepine antagonist RO 15-1788 completely counteracted the anxiolytic effects of clorazepate dosed at 2.0 mg/kg and the anxiogenic effects of beta-CCM, which failed to present sedative or postictal depressive effects.
PsychopharmacologyCharacteristic behavioral alterations in rats induced by rolipram and other selective adenosine cyclic 3?,5?-monophosphate phosphodiesterase inhibitors
138 Citations1982H. Wachtel
Comparatively high doses of the alkylxanthine PDE inhibitors IBMX and theophylline caused hypothermia, forepaw shaking, grooming, and head twitches concomitantly with a decline of the motor stimulatory effect, suggesting enhanced availability of brain cAMP.
Comparative Biochemistry and Physiology Part C Comparative PharmacologyThe effect of various centrally active drugs on adenosine uptake by the central nervous system
136 Citations1982John W. Phillis, P.H. Wu
It is proposed that many agents with anxiolytic, sedative, analgesic or anti-convulsant actions may achieve their effects by inhibiting adenosine uptake and thus potentiating extracellularadenosine levels.
Behavioural ProcessesBehavioural Validation of a Light/Dark Choice Procedure for Testing Anti-Anxiety Agents
98 Citations1989Rend Misslin, Catherine Belzung +1 more
The present results indicate that this procedure can be considered as an unconditioned conflict paradigm based at once on the innate tendency of mice to seek refuge in a dark box and their propensity to escape novel places into which they have been forced.
Biochimica et Biophysica Acta (BBA) - General SubjectsAssessment of selective inhibition of rat cerebral cortical calcium-independent and calcium-dependent phosphodiesterases in crude extracts using deoxycyclic AMP and potassium ions
75 Citations1984Christopher J. Davis
The specificity of potassium ions in inhibiting the activity of the calcium-dependent phosphodiesterase and deoxycyclic AMP in inhibitediting the calcine-independent enzyme was found to provide a convenient means to assess the effects of agents on these activities in crude extracts of cerebral cortex.
Brain ResearchAutoradiographic mapping of a selective cyclic adenosine monophosphate phosphodiesterase in rat brain with the antidepressant [3H]rolipram
63 Citations1989P. Kaulen, G. Brünning +3 more
Biochemical PharmacologySelective inhibition of one of the cyclic AMP phosphodiesterases from rat brain by the neurotropic compound rolipram
55 Citations1985Georges Némoz, Annie‐France Prigent +4 more
Naunyn-Schmiedeberg s Archives of PharmacologyRolipram, a stereospecific inhibitor of calmodulin-independent phosphodiesterase, causes?-adrenoceptor subsensitivity in rat cerebral cortex
54 Citations1986Joachim E. Schultz, Bernard Schmidt
It is suggested that stereospecific and isozyme specific inhibition of cAMP-phosphodiesterase is, at least in part, related to the mechanism of action of the potential antidepressant drug rolipram and possibly of other antidepressants as well.
Journal of Pharmacy and PharmacologyNeurotropic effects of the optical isomers of the selective adenosine cyclic 3′,5′-monophosphate phosphodiesterase inhibitor rolipram in rats in-vivo
44 Citations1983H. Wachtel
It is suggested that (+)‐rolipram is a less potent neurotropic PDE inhibitor in‐vivo than its (‐)‐enantiomer.
Pharmacology Biochemistry and BehaviorAntidepressant effects of rolipram in a genetic animal model of depression: Cholinergic supersensitivity and weight gain
42 Citations1989David H. Overstreet, Kay L. Double +1 more
The FSL rats, which are genetically supersensitive to cholinergic agonists, are even more sensitive following chronic treatment with ro Lipram, suggesting that rolipram may not be appropriate as an antidepressant for humans because of undesirable side effects.
Journal of Medicinal ChemistrySynthesis and enzymic activity of various substituted pyrazolo[1,5-a]-1,3,5-triazines as adenosine cyclic 3',5'-phosphate phosphodiesterase inhibitors
30 Citations1982K. SENGA, Darrell E. O'Brien +4 more
The most active compound was 8-bromo-4-(diethylamino)-7-phenylpyrazolo[ 1,3-a]-1,3,5-triazine, which was 185 times more potent than theophylline as an inhibitor of PDE isolated from rabbit lung.
Pharmacology Biochemistry and BehaviorAnxiolytic and sedative properties of BW A78U, a novel anticonvulsant adenine derivative
10 Citations1990Marc Willard, René Misslin +4 more
The data show that BW A78U possesses some of the characteristic properties of the minor tranquilizers, but since this compound binds to the benzodiazepine receptor with a very low affinity, it can be assumed that this drug does not exert its behavioral effects through these receptors.