Abstract
The dose-response effects of the substituted xanthine 8-cyclopropyltheophylline (CPRT) on sleep and wakefulness (W) after intraperitoneal administration to rats were examined by means of simultaneous electroencephalographic (EEG) and electromyographic (EMG) recordings. Doses of 20 and 40 mg/kg CPRT increased W and decreased slow wave sleep (SWS) in rats, indicating CNS stimulant effects. The greatest CNS stimulation was produced by the lowest (20 mg/kg) dose of CPRT examined, which also increased the latency to SWS. In addition, the 20 mg/kg dose of CPRT also significantly decreased the amount of total sleep (TS), as compared to the vehicle group, during all time periods examined. In contrast, the 80 mg/kg dose of CPRT decreased W and increased both SWS and TS. However, this apparent hypnotic effect of the 80 mg/kg CPRT may be due to toxicity, since 80% of rats treated with this dose of the drug died within 48 h of injection.
Similar content being viewed by others
References
Bruns RF, Lu GH, Pugsley TA (1986) Characterization of the A2 adenosine receptor labelled by [3H]NECA in rat striatal membranes. Mol Pharmacol 29:331–346
Bruns RF, Lu GH, Pugsley TS (1987a) Adenosine receptor subtypes: binding studies. In: Gerlach E, Becker BF (eds) Topics and perspectives in adenosine research. Springer, Berlin Heidelberg New York, pp 59–73
Bruns RF, Fergus JH, Badger EW, Bristol JA, Santay LA, Hartman JD, Hays SJ, Huang CC (1987b) Binding of the A1 adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine to rat brain membranes. Naunyn-Schmiedeberg's Arch Pharmacol 335:59–63
Daly JW, Butts-Lamb P, Padgett W (1983) Subclasses of adenosine receptors in the central nervous system: interaction with caffeine and related methylxanthines. Cell Mol Neurobiol 3:69–80
Daly JW, Ukena D, Jacobson KA (1987) Analogs of adenosine, theophylline, and caffeine: selective interactions with A1 and A2 adenosine receptors. In: Gerlach E, Becker BF (eds) Topics and perspectives in adenosine research. Springer, Berlin Heidelberg New York, pp 23–35
Dietz AJ, Burgison RM (1966) The synthesis and pharmacologic evaluation of a series of 8-alkylthio-thiated theophyllines. J Med Chem 9:50–57
Goodsell EB, Stein HH, Wenzke KJ (1971) 8-Substituted theophyllines. In vitro inhibition of 3′,5′-cyclic adenosine, monophosphate phosphodiesterase and pharmacological spectrum in mice. J Med Chem 14:1202–1205
Londos C, Cooper DMF, Wolff J (1980) Subclasses of external adenosine receptors. Proc Natl Acad Sci USA 77:2551–2554
Martinson EA, Johnson RA, Wells JN (1987) Potent adenosine receptor antagonists that are selective for the A1 adenosine receptor subtype. Mol Pharmacol 31:247–252
Meyers RD (1978) Psychopharmacology of alcohol. Annu Rev Pharmacol Toxicol 18:125–144
Phillis JW, Wu PH (1981) The role of adenosine and its nucleotides in central synaptic transmission. Prog Neurobiol 16:187–239
Radulovacki M, Virus RM, Djuricic-Nedelson M, Green RD (1983) Hypnotic effects of deoxycoformycin in rats. Brain Res 271:392–395
Radulovacki M, Virus RM, Djuricic-Nedelson M, Green RD (1984) Adenosine analogs and sleep in rats. J Pharmacol Exp Ther 228:268–274
Radulovacki M, Virus RM, Rapoza D, Crane RA (1985) A comparison of the dose-response effects of pyrimidine ribonucleosides and adenosine on sleep in rats. Psychopharmacology 87:136–140
Snyder SH, Katims JH, Annau Z, Bruns RF, Daly JW (1981) Adenosine receptors and behavioral actions of methylxanthines. Proc Natl Acad Sci USA 78:3260–3264
Sokal RR, Rohlf FJ (1981) Biometry, 2nd ed. Freeman, San Francisco
Van Calker D, Muller M, Hamprecht B (1979) Adenosine regulates via two different types of receptors, the accumulation of cyclic AMP in cultured brain cells. J Neurochem 33:999–1005
Virus RM, Djuricic-Nedelson M, Radulovacki M, Green RD (1983) The effects of adenosine and 2′-deoxycoformycin
Yanik G, Glaum S, Radulovacki M (1987) The dose-response effects of caffeine on sleep in rats. Brian Res 403:177–180
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Radulovacki, M., Virus, R.M. Dose-response effects of 8-cyclopropyltheophylline on sleep and wakefulness in rats. Psychopharmacology 94, 417–420 (1988). https://doi.org/10.1007/BF00174700
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00174700