Abstract
Biologically active n-acylprolyl-dipeptides were described by us recently. GVS-111 was shown to be one of the more active substances of this series.
The effects of the GVS-111 on diazepam withdrawal were studied in male Wistar rats treated for 21 days with diazepam 4 mg/kg/day (i.p.). The withdrawal syndrome was assessed 24 hours after the last diazepam injection. Withdrawal signs recorded were: anxiogenic - like behavior in the elevated plus maze (EPM), suppression of exploratory behavior in the open field and the intensification of seizures, precipitated by pentylentetrazol. Two regimes of administration of GVS-111 (0.5 mg/kg, i.p) were used: a) during withdrawal 15 minutes before testing in above mentioned paradigms, b) during last 7 days of diazepam administration and during withdrawal. GVS-111 was demonstrated to be able to attenuate the degree of anxiogenic state in EPM, dramatically increasing time spent in open arms. GVS-111 decreased the degree of pentylentetrazol precipitated seizures. There was no significant effects upon the activity in open field. All these effects of GVS-111 were more pronounced in case of long-term administration. These findings suggest that GVS-111 may have potential as a treatment for withdrawal from sedative/hypnotics.
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Seredenin, S., Garibova, T., Halikas, J. et al. Effects of Novel Substituted Prolyldipeptide, GVS-111, on Benzodiazepine Wiithdrawal in Rats. Neuropsychopharmacol 11, 283 (1994). https://doi.org/10.1038/sj.npp.1380205
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DOI: https://doi.org/10.1038/sj.npp.1380205