Summary
Naloxone in high doses (60–240 mg/kg i.p.) produced a dose-dependent increase in cerebellar cGMP content of mice. The rise in cGMP content reached its maximum within 5 min and was of short duration. Short-lasting episodes of clonic seizures were noted after 240 mg/kg naloxone. Low doses of naloxone (5–10 mg/kg) had no effect on cerebellar cGMP content, but markedly potentiated the increase in cGMP induced by diazepam, but had only a slight effect on the action of pentobarbital (30 mg/kg i.p.).
These results support the assumption proposed by other authors that naloxone exerts GABA antagonistic effects aside from the potent opiate receptor antagonistic activity.
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References
Bell, E. F.: The use of naloxone in the treatment of diazepam poisoning. J. Pediatr. 87, 803–804 (1975)
Biggio, G., Costa, E., Guidotti, A.: Pharmacologically induced changes in the 3′,5′-cyclic guanosine monophosphate content of rat cerebellar cortex: Differences between apomorphine, haloperidol and harmaline. J. Pharmacol. Exp. Ther. 200, 207–215 (1977)
Breuker, E., Dingledine, R., Iversen, L. L.: Evidence for naloxone and opiates as GABA antagonists. Br. J. Pharmacol. 58, 458 P (1976)
Costa, F., Guidotti, A., Mao, C. C.: Evidence for involvement of GABA in the action of benzodiazepines: Studies on rat cerebellum. Adv. Biochem. Pharmacol. 14, 113–130 (1975a)
Costa, E., Guidotti, A., Mao, C. C., Suria, A.: New concept on the mechanism of action of benzodiazepines. Life Sci. 17, 167–186 (1975b)
Costa, E., Guidotti, A., Mao, C. C.: A GABA hypothesis for the action of benzodiazepines in CNS. In: Nervous system function. (E. Roberts, T. N. Chase and D. B. Tower, eds.), pp. 413–426. New York: Raven Press 1976
Dingledine, R., Iversen, L. L., Breuker, E.: Naloxone as a GABA antagonist: Evidence from iontophoretic, receptor binding and convulsant studies. Eur. J. Pharmacol. 47, 19–28 (1978)
Dinnendahl, V.: A rapid and simple procedure for the determination of guanosien 3′,5′-monophosphate by use of the protein binding method. Naunyn-Schmiedeberg's Arch. Pharmacol. 284, 55–61 (1974)
Dinnendahl, V., Gumulka, S. W.: Stress-induced alterations of cyclic nucleotide levels in brain: Effects of centrally acting drugs. Psychopharmacology 52, 243–249 (1977)
Fürst, Z., Foldes, F. F., Knoll, J.: The influence of naloxone on barbiturate anesthesia and toxicity in the rat. Life Sci. 20, 921–926 (1977)
Fuxe, K., Agnati, L. F., Bolme, P., Hökfelt, T., Lidbrink, P., Ljungdahl, A., de la Mora, M. P., Ögren, S. O.: The possible involvement of GABA mechanisms in the action of benzodiazepines on central catecholamine neurons. Adv. Biochem. Psychopharmacol. 14, 45–61 (1975)
Govoni, S., Fresia, P., Spano, P. F., Trabucchi, M.: Effect of desmethyldiazepam and chlordesmethyldiazepam on 3′,5′-cyclic guanosine monophosphate levels in rat cerebellum. Psychopharmacology 50, 241–244 (1976)
Haefely, W., Kulcsár, A., Möhler, H., Pieri, L., Pole, P., Schaffner, R.: Possible involvement of GABA in the central actions of benzodiazepines. Adv. Biochem. Psychopharmacol. 14, 131–152 (1975)
Mao, C. C., Guidotti, A., Costa, E.: The regulation of cyclic guanosine monophosphate in rat cerebellum: Possible involvement of putative amino acid transmitters. Brain Res. 79, 510–514 (1974a)
Mao, C. C., Guidotti, A., Costa, E.: Interactions between γ-aminobutyric acid and guanosine cyclic-3′,5′-monophosphate in rat cerebellum. Mol. Pharmacol. 10, 736–745 (1974b)
Mao, C. C., Guidotti, A., Costa, E.: Evidence for an involvement of GABA in the mediation of the cerebellar cGMP decrease and the anticonvulsant action of diazepam. Naunyn-Schmiedeberg's Arch. Pharmacol. 289, 369–378 (1975)
Opmeer, F. A., Gumulka, S. W., Dinnendahl, V., Schönhöfer, P. S.: Effects of stimulatory and depressant drugs on cyclic guanosine 3′,5′-monophosphate and adenosine-3′,5′-monophosphate levels in mouse brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 292, 259–265 (1976)
Polc, P., Mohler, H., Haefely, W.: The effect of diazepam on spinal cord activities: Possible sites and mechanisms of action. Naunyn-Schmiedeberg's Arch. Pharmacol. 284, 319–337 (1974)
Ransom, B. R., Baker, J. L.: Pentobarbital selectively enhances GABA-mediated post-synaptic inhibition in tissue cultured mouse spinal neurons. Brain Res. 114, 530–535 (1976)
Suria, A., Costa, E.: Evidence for GABA involvement in the action of diazepam on presynaptic nerve terminals in bulfrog sympathetic ganglia. Adv. Biochem. Psychopharmacol. 14, 103–112 (1975)
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Gumulka, S.W., Dinnendahl, V. & Schönhöfer, P.S. The effect of naloxone on cerebellar cGMP content. Naunyn-Schmiedeberg's Arch. Pharmacol. 306, 169–172 (1979). https://doi.org/10.1007/BF00498987
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DOI: https://doi.org/10.1007/BF00498987