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. 1972 Feb;44(2):262–270. doi: 10.1111/j.1476-5381.1972.tb07262.x

Uptake of desipramine by the rat vas deferens

R Binini, A Bonaccorsi, S Garattini, P L Morselli, G Muscettola
PMCID: PMC1666043  PMID: 4668593

Abstract

1. Determinations of desipramine in the isolated rat vas deferens were carried out in order to study the uptake of the drug and to evaluate how this may correlate with the effect on noradrenaline (NA)-induced contraction.

2. Vasa deferentia, in contact with concentrations of desipramine of 1 ng-25 μg/ml for 10 min accumulated the drug about 6-fold in respect to the medium. When the time of contact was prolonged to 4 h, desipramine (200 ng/ml) was concentrated about 100-fold. The uptake was not saturable and it was not affected by the presence of imipramine, cocaine, ouabain, dinitrophenol and iodoacetate.

3. No metabolic process is involved although the accumulation of desipramine is temperature dependent. The release of desipramine from the vas deferens is exponential and it is not affected by the presence of plasma in the medium.

4. No clear correlation was found between tissue concentration of the drug and the potentiation of noradrenaline responses, probably because of the high non-specific binding of the drug to tissue components which may mask specific binding sites for NA resulting in potentiation. However, the concentration of desipramine seems to correlate with the inhibition of NA effect which occurs at high doses of desipramine.

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Selected References

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

  1. Birmingham A. T. Sympathetic denervation of the smooth muscle of the vas deferens. J Physiol. 1970 Mar;206(3):645–661. doi: 10.1113/jphysiol.1970.sp009035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bonaccorsi A., Jespersen J., Garattini S. The influence of desipramine on the sensitivity and accumulation of noradrenaline in the isolated tail artery of the rat. Eur J Pharmacol. 1970 Jan;9(1):124–127. doi: 10.1016/0014-2999(70)90331-6. [DOI] [PubMed] [Google Scholar]
  3. Borgå O., Azarnoff D. L., Sjöqvist F. Species differences in the plasma protein binding of desipramine. J Pharm Pharmacol. 1968 Jul;20(7):571–571. doi: 10.1111/j.2042-7158.1968.tb09809.x. [DOI] [PubMed] [Google Scholar]
  4. DINGELL J. V., SULSER F., GILLETTE J. R. SPECIES DIFFERENCES IN THE METABOLISM OF IMIPRAMINE AND DESMETHYLIMIPRAMINE (DMI). J Pharmacol Exp Ther. 1964 Jan;143:14–22. [PubMed] [Google Scholar]
  5. Gillette J. R. Biochemistry of drug oxidation and reduction by enzymes in hepatic endoplasmic reticulum. Adv Pharmacol. 1966;4:219–261. doi: 10.1016/s1054-3589(08)60100-3. [DOI] [PubMed] [Google Scholar]
  6. Hammer W. M., Brodiet B. B. Application of isotope derivative technique to assay of secondary amines: estimation of desipramine by acetylation with H3-acetic anhydride. J Pharmacol Exp Ther. 1967 Sep;157(3):503–508. [PubMed] [Google Scholar]
  7. Kuschinsky K., Lahrtz H., Lüllmann H., van Zwieten P. A. Accumulation and release of 3H-digoxin by guinea-pig heart muscle. Br J Pharmacol Chemother. 1967 Jun;30(2):317–328. doi: 10.1111/j.1476-5381.1967.tb02138.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lewis J. E., Miller J. W. The use of tritiated phenoxybenzamine for investigating receptors. J Pharmacol Exp Ther. 1966 Oct;154(1):46–55. [PubMed] [Google Scholar]
  9. Marks B. H., Dutta S., Hoffman R. F. Cocaine-H3 binding by the isolated guinea pig vas deferens. Arch Int Pharmacodyn Ther. 1967 Jul;168(1):28–35. [PubMed] [Google Scholar]
  10. Matsuo S., Toda N. The influence of desmethylimipramine on the chronotropic response to endogenous and exogenous noradrenaline in the isolated atria. Br J Pharmacol Chemother. 1968 Mar;32(3):473–482. doi: 10.1111/j.1476-5381.1968.tb00448.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Moran J. F., May M., Kimelberg H., Triggle D. J. Studies on the noradrenaline alpha-receptor. I. Techniques of receptor isolation. The distribution and specificity of action of N-(2-bromoethyl)-N-ethyl-1-naphthylmethylamine, a competitive antagonist of noradrenaline. Mol Pharmacol. 1967 Jan;3(1):15–27. [PubMed] [Google Scholar]
  12. PATON W. D., RANG H. P. THE UPTAKE OF ATROPINE AND RELATED DRUGS BY INTESTINAL SMOOTH MUSCLE OF THE GUINEA-PIG IN RELATION TO ACETYLCHOLINE RECEPTORS. Proc R Soc Lond B Biol Sci. 1965 Aug 24;163:1–44. doi: 10.1098/rspb.1965.0058. [DOI] [PubMed] [Google Scholar]
  13. Patil P. N., LaPidus J. B., Tye A. Steric aspects of adrenergic drugs. I. Comparative effects of DL isomers and desoxy derivatives. J Pharmacol Exp Ther. 1967 Jan;155(1):1–12. [PubMed] [Google Scholar]
  14. Potter L. T. Uptake of propranolol by isolated guinea-pig atria. J Pharmacol Exp Ther. 1967 Jan;155(1):91–100. [PubMed] [Google Scholar]
  15. Sjöqvist F., Berglund F., Borgå O., Hammer W., Andersson S., Thorstrand C. The pH-dependent excretion of monomethylated tricyclic antidepressants. Clin Pharmacol Ther. 1969 Nov-Dec;10(6):826–833. doi: 10.1002/cpt1969106826. [DOI] [PubMed] [Google Scholar]
  16. URSILLO R. C., JACOBSON J. POTENTIATION OF NOREPINEPHRINE IN THE ISOLATED VAS DEFERENS OF THE RAT BY SOME CNS STIMULANTS AND ANTIDEPRESSANTS. J Pharmacol Exp Ther. 1965 May;148:247–251. [PubMed] [Google Scholar]

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