Skip to main content
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1985 May;19(5):639–647. doi: 10.1111/j.1365-2125.1985.tb02691.x

Comparison of the effects of chronic administration of ciclazindol and desipramine on pupillary responses to tyramine, methoxamine and pilocarpine in healthy volunteers.

F A Kerr, E Szabadi
PMCID: PMC1463841  PMID: 4005103

Abstract

Twenty-nine healthy volunteers participated in an experiment lasting for 8 weeks: Phase I (2 weeks)--pre-treatment control period; Phase II (4 weeks)--medication with either ciclazindol hydrochloride (50 mg twice daily), or desipramine hydrochloride (50 mg twice daily) or lactose placebo (twice daily) administered in a single-blind fashion; Phase II (2 weeks)--recovery. Experimental sessions took place twice weekly for the photographic assessment of resting pupil diameter, and for the assessment of one of the following pupillary responses: mydriatic response to methoxamine, mydriatic response to tyramine, miotic response to pilocarpine. Resting pupil diameter increased during medication with either ciclazindol or desipramine. Methoxamine-evoked mydriasis and tyramine-evoked mydriasis were antagonized by both ciclazindol and desipramine. Pilocarpine-evoked miosis was potentiated by both ciclazindol and desipramine. The steady-state plasma levels (mean +/- s.e. mean) of the antidepressants were: ciclazindol: 5.90 +/- 0.74 microM; desipramine: 0.60 +/- 0.17 microM. The antagonism of methoxamine-evoked mydriasis is likely to reflect the blockade of postsynaptic alpha 1-adrenoceptors in the iris by the antidepressants, whereas the antagonism of tyramine-evoked mydriasis may reflect both the blockade of uptake of tyramine into presynaptic adrenergic terminals and the blockade of postsynaptic alpha-adrenoceptors. There is no immediate explanation for the potentiation of pilocarpine-evoked miosis by the two antidepressants.

Full text

PDF
642

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Carnis G., Godbillon J., Metayer J. P. Determination of clomipramine and desmethyl-clomipramine in plasma or urine by the double-radioisotope derivative technique. Clin Chem. 1976 Jun;22(6):817–823. [PubMed] [Google Scholar]
  2. Ehsanullah R. S., Kirby M. J., Leighton M., Oh V. M. Some clinical pharmacological studies with ciclazindol hydrochloride [proceedings]. Br J Clin Pharmacol. 1977 Jun;4(3):400P–400P. [PubMed] [Google Scholar]
  3. Ghose K., Rama Rao V. A., Bailey J., Coppen A. Antidepressant activity and pharmacological interactions of ciclazindol. Psychopharmacology (Berl) 1978 Apr 14;57(1):109–114. doi: 10.1007/BF00426966. [DOI] [PubMed] [Google Scholar]
  4. Kerr F. A., Szabadi E. Interaction of desipramine and ciclazindol with adrenergic mechanisms in the human iris [proceedings]. Br J Clin Pharmacol. 1979 Oct;8(4):396P–397P. [PubMed] [Google Scholar]
  5. Kirby M. J., Turner P. Ciclazindol and mazindol on glucose uptake into human isolated skeletal muscle: no interaction of mazindol with methysergide. Br J Clin Pharmacol. 1977 Aug;4(4):459–461. doi: 10.1111/j.1365-2125.1977.tb00762.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Langer S. Z. Presynaptic regulation of the release of catecholamines. Pharmacol Rev. 1980 Dec;32(4):337–362. [PubMed] [Google Scholar]
  7. Lean M. E., Borthwick L. J. Ciclazindol: an oral agent with weight reducing properties and hypoglycaemic activity. Eur J Clin Pharmacol. 1983;25(1):41–45. doi: 10.1007/BF00544012. [DOI] [PubMed] [Google Scholar]
  8. Rudorfer M. V., Young R. C. Anticholinergic effects and plasma desipramine levels. Clin Pharmacol Ther. 1980 Nov;28(5):703–706. doi: 10.1038/clpt.1980.224. [DOI] [PubMed] [Google Scholar]
  9. Shur E., Checkley S. Pupil studies in depressed patients: an investigation of the mechanism of action of desipramine. Br J Psychiatry. 1982 Feb;140:181–184. doi: 10.1192/bjp.140.2.181. [DOI] [PubMed] [Google Scholar]
  10. Sneddon J. M., Turner P. The interactions of local guanethidine and sympathomimetic amines in the human eye. Arch Ophthalmol. 1969 May;81(5):622–627. doi: 10.1001/archopht.1969.00990010624005. [DOI] [PubMed] [Google Scholar]
  11. Snyder S. H., Yamamura H. I. Antidepressants and the muscarinic acetylcholine receptor. Arch Gen Psychiatry. 1977 Feb;34(2):236–239. doi: 10.1001/archpsyc.1977.01770140126014. [DOI] [PubMed] [Google Scholar]
  12. Sugden R. F. The action of indoramin and other compounds on the uptake of neurotransmitters into rat cortical slices. Br J Pharmacol. 1974 Jul;51(3):467–469. doi: 10.1111/j.1476-5381.1974.tb10687.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Swaisland A. J., Franklin R. A., Southgate P. J., Coleman A. J. The pharmacokinetics of ciclazindol (Wy 23409) in human volunteers. Br J Clin Pharmacol. 1977 Feb;4(1):61–65. doi: 10.1111/j.1365-2125.1977.tb00668.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Szabadi E., Besson J., Bradshaw C. M. Pupil responsiveness to tyramine in depressed patients treated with amitriptyline. Br J Clin Pharmacol. 1975 Aug;2(4):362–363. doi: 10.1111/j.1365-2125.1975.tb02787.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Szabadi E., Gaszner P., Bradshaw C. M. Interaction of desipramine and amitriptyline with adrenergic mechanisms in the human iris in vivo. Eur J Clin Pharmacol. 1981;19(6):403–408. doi: 10.1007/BF00548582. [DOI] [PubMed] [Google Scholar]
  16. Szabadi E., Gaszner P., Bradshaw C. M. The peripheral anticholinergic activity of tricyclic antidepressants: comparison of amitriptyline and desipramine in human volunteers. Br J Psychiatry. 1980 Nov;137:433–439. doi: 10.1192/bjp.137.5.433. [DOI] [PubMed] [Google Scholar]
  17. Szabadi E. The influence of the baseline on the size of pharmacological responses: a theoretical model [proceedings]. Br J Pharmacol. 1977 Nov;61(3):492P–493P. [PMC free article] [PubMed] [Google Scholar]
  18. Waterfall J. F., Smith M. A., Gaston W. H., Maher J., Warburton G. Cardiovascular and autonomic actions of ciclazindol and tricyclic antidepressants. Arch Int Pharmacodyn Ther. 1979 Jul;240(1):116–136. [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES