Psychopharmacology

, Volume 85, Issue 2, pp 129–132 | Cite as

Effects of some dibenzo-azepines on suppressed and nonsuppressed behavior of squirrel monkeys

  • Roger D. Spealman
Original Investigations

Abstract

Six dibenzo-azepine derivatives were compared for their effects on suppressed and nonsuppressed behavior of squirrel monkeys. Monkeys responded by pressing a lever under a two-component fixed-ratio schedule of food presentation in which responding in one component was suppressed by response-produced electric shock. Intermediate doses (0.3–1.0 mg/kg IM) of selected unsubstituted and 8-chlorine-substituted dibenzo-azepines (perlapine, 106-094, and clozapine) increased responding that was suppressed by electric shock, whereas selected 2-chlorine-substituted dibenzo-azepines (loxapine, clothiapine, and 105-056) did not consistently increase suppressed responding at any dose (0.001–0.1 mg/kg IM). All six dibenzo-azepines decreased nonsuppressed responding in a dose-related manner, with the 2-chlorine-substituted derivatives being 16–50 times more potent than their unsubstituted or 8-chlorine-substituted congeners. These structure-activity relationships indicate that the effects of the dibenzo-azepines on both suppressed and nonsuppressed behavior differ qualitatively depending on the location of the chlorine substituent.

Key words

Dibenzo-azepines Suppressed behavior Schedule-controlled behavior Fixed-ratio schedule Squirrel monkeys 

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References

  1. Blum A, Girke W (1973) Marked increase in REM sleep produced by a new antipsychotic compound. Clin Electroencephalogy 4: 80–84Google Scholar
  2. Bürki HR, Ruch W, Asper H (1975) Effects of clozapine, thioridazine, perlapine and haloperidol on the metabolism of biogenic amines in the brain of the rat. Psychopharmacology 41: 27–33Google Scholar
  3. Bürki HR, Ruch W, Asper H, Baggiolini M, Stille G (1974) Effect of a single and repeated administration of clozapine on the metabolism of dopamine and noradrenaline in the brain of the rat. Eur J Pharmacol 27: 180–190Google Scholar
  4. DeMaio D (1972) Clozapine, a novel major tranquilizer. Arzneim Forsch 22: 919–921Google Scholar
  5. Dews PB (1981) Behavioral pharmacology of anxiolytics. In: Hoffmeister F, Stille G (eds) Handbook of experimental pharmacology, vol 55/II. Springer, Heidelberg, pp 285–292Google Scholar
  6. Sayers AC, Amsler HA (1977) Clozapine. In: Goldberg ME (ed) Pharmacological and biochemical properties of drug substances, vol 1. Am Pharm Assn, Washington DC, pp 1–31Google Scholar
  7. Schmutz J (1975) Neuroleptic piperazinyl-dibenzo-azepines. Arzneim Forsch 25: 712–720Google Scholar
  8. Sepinwall J, Cook L (1980) Mechanism of action of the benzodiazepines: behavioral aspect. Fed Proc 39: 3024–3031Google Scholar
  9. Spealman RD (1979) Comparison of drug effects on responding punished by pressurized air or electric shock delivery in squirrel monkeys: pentobarbital, chlordiazepoxide, d-amphetamine and cocaine. J Pharmacol Exp Ther 209: 309–315Google Scholar
  10. Spealman RD, Katz JL (1980) Some effects of clozapine on punished responding by mice and squirrel monkeys. J Pharmacol Exp Ther 212: 435–440Google Scholar
  11. Spealman RD, Kelleher RT, Goldberg SR, DeWeese J, Goldberg DM (1983) Behavioral effects of clozapine: comparison with thioridazine, chlorpromazine, haloperidol and chlordiazepoxide in squirrel monkeys. J Pharmacol Exp Ther 224: 127–134Google Scholar
  12. Stille G, Sayers A, Lauener H, Eichenberger E (1973) 6-(4-Methyl-1-piperazinyl) morphanthridine (perlapine), a new tricyclic compound with sedative and sleep-promoting properties. Psychopharmacology 28: 325–337Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • Roger D. Spealman
    • 1
  1. 1.Laboratory of Psychobiology, Department of Psychiatry, Harvard Medical SchoolBoston and New England Regional Primate Research CenterSouthboroughUSA

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