Scientific Online Resource System

Scripta Scientifica Medica

EFFECT OF ISOTEOLINE IN ANIMAL MODELS PREDICTIVE OF ANTIDEPRESSANT ACTIVITY

M. Zhelyazkova-Savova, S. Valcheva-Kuzmanova, D. K. Zhelyazkov

Abstract

Isoteoline, a compound of aporphine structure, was studied for antidepressant activity. Two animal models were used: the behavioral despair test and the clonidine-induced hypothermia. Isoteoline failed to alter the immobility time in rats subjected to forced swimming, but antagonized the immobility-reducing effect of desipramine, both after a single and multiple administration. In rats made hypothermic by i.p. injection of clonidine, Isoteoline did not antagonize the effect on rectal temperature, but rather accentuated it. The conclusion was made that Isoteoline was devoid of antidepressant activity. The results were analyzed in terms of previously demonstrated interactions of Isoteoline with subtypes of serotonergic receptors and were found to provide further evidence in support of these interactions.


Keywords

isoteoline; behavioral despair test; clonidine-induced hypothermia; antidepressant activity; rats

Full Text


References

Желязков, Д . , H. Моллов, М. Марков, X. Филипов и д р . Средство за лечение на хипертонична болест и метод за неговата синтеза. Авт. свид. №43200/ 13. IV. I984 r. МПК А61 31/485. Държ. per. №55261/1982.

Желязкова-Савова, М. Влияние изотеолина на поведение мышей в условиях теста для выявляння анксиолитической активности. - Экс перни. клин. фармакол., 61, 1998. № 3, 19-21.

Марков. М.. Д. Желязков. Н. Георгиев. Антихипертензивен ефект на изотеолина при моделни хипертонии. - Експерим. мед. морфол., 1984, № 3, 134-138.

Ceivo, L ., G . Grignaschi, R . Samanin. 8-Hydroxy-2-(di- -propylamino) tetralin. a selective 5-HT IA receptor agonist, reduces the iinmiobility of rats in the forced swimming test by acting on the nucleus raphe dorsalis.- Eur. J. Pharmacol., 158, 1988, 53-59.

Curzon, G . , G. A. Kennet. m-CPP: a tool for studying behavioural responses associated with 5-HT 1С receptors.- Trends Pharmacol. Sci., 11, 1990, 181-182.

Danysz, W.. A. Plaznik , W. Kostowski , E. Malatynska el al. Comparison of desipramine, amitriptyline, zimelidine and alaproctate in six animal models used to investigate antidepressant drugs.- Pharmacol. Toxicol., 62, 1988, 42-50.

Espejo, E. F., F. J. Minano. Prefrontocortical dopamine depletion induces antidepressant-like effects in rats and alters the profile of desipramine during Porsolt's test.- Neuroscience, 88, 1999, 609-615.

Kitada, Y . , T . Miyauchi, Y . Kanazawa, H. Nakamichi et al. Involvement of alpha- and beta 1- adrenergic mechanisms in the immobility-reducing action of desipramine in the forced swimming test.- Seuropharmacolog): 22, 1983, 1055-1060.

Leonard, В. E . Mechanisms of action of antidepressants.- CMS Drugs, 4, 1995, Suppl. 1, 1-12.

Millan , M. J. , A . Dekeyne. A . Gobert. Serotonin (5-HT)2C receptors tonically inhibit dopamine (DA) and noradrenaline (NA), but not serotonin, release in the frontal cortex in vivo.- Neuropharmacology, 37, 1998, 953-955.

Pehek. E . A . Local infusion of of the serotonin antagonists ritanserin or ICS 205,930 increases in vivo dopamine release in the rat medial prefrontal cortex.- Synapse, 24, 1996, 12-18.

Plaznik, A . , W. Kostowski , W. Danysz. The involvement of brain serotonin in the clonidine- induced hypothermia in rats.- Pol. J. Pharmacol. Pharm.. 35, 1983, 301-308.

Porsolt, R. D . , G . Anton, N . Blavet , M. Jalfre . Behavioral despair in rats: a new model sensitive to antidepressant treatments.- Eur. J. Pharmacol., 47, 1978,379-391.

Sanchez, C , J . Ну tte I . Comparison of the effects of antidepressants and their metabolites on the reuptake of biogenic amines and on receptor binding.- Cell. Mol. Seurobiol. 19, 1999,467-489.

Suhara, Т., О. Inoue, К.. Kobayasi . Effect of desipramine on dopamine receptor binding in vivo.- Life Sci., 47, 1990, 2119-2126.

Valiente. M., S. Martinez. M. D. Ivorra , B. К. Casse I s et al. Functional study on rat aorta and tail artery of a series of aporphine derivatives showing selective affinity for alpha-1A adrenoceptors.- Saunyn-Schmiadeberg's Arch. Pharmacol.. 351, 1998, Suppl. 2. R605.

Zhelyazkov. D., M. Markov, A. Maleeva, N. Visheva et al. Neuro-endocrine effects of isoteoline.- Acta Physiol. Pharmacol. Bulg., 10, 1984. No 4, 53-58.

Zhelyazkova-Savova, M. Isoteoline in two models of serotonin 5-HT2C receptor stimulation.- Annu. Proc. IMAB, 4, 1998, No 2, 297-299.

Zhelyazkova-Savova , M. Effects of isoteoline in two animal models of anxiety in the rat.- Annu. Proc. IMAB. 5, 1999, No 2, 240-242.

Zhelyazkova-Savova, M., N. Negrev. Isoteoline, a putative serotonin antagonist, inhibits m-CPP, but not 8-OH-DPAT and DOI-induced increase in serum prolactin levels.- Pharmacol. Res., 42, 2000, 93-96.




DOI: http://dx.doi.org/10.14748/ssm.v34i0.2780

Refbacks

Article Tools
Email this article (Login required)
About The Authors

M. Zhelyazkova-Savova

S. Valcheva-Kuzmanova

D. K. Zhelyazkov

Font Size


|