Drugs online research references
Neurosci Lett. 1992 May 11;139(1):69-72.
Serotonin uptake inhibition: in vivo effect of sertraline in rats.
Manfridi A, Clavenna A, De Simoni MG.
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Sertraline, a potent and selective serotonin uptake inhibitor, was used to analyze the changes occurring in the serotonin system after uptake inhibition in vivo. Sertraline (11 mg/kg) lowered extracellular 5-hydroxyindolacetic acid (5-HIAA), measured in rat hippocampus by in vivo voltammetry, for about 3 h. The interaction between sertraline and drugs known to interfere with the release or uptake of serotonin (L-5-hydroxytryptophan (5-HTP), d-norfenfluramine and tianeptine) was then studied. The sertraline-induced decrease in extracellular 5-HIAA was related to the inhibition of uptake.
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J Neural Transm Gen Sect. 1992;88(2):143-56.
Effects of sertraline and citalopram given repeatedly on the responsiveness of 5-HT receptor subpopulations.
Maj J, Moryl E.
Institute of Pharmacology, Polish Academy of Sciences, Krakow.
The effect of repeated treatment (5 and 10 mg/kg, po, twice daily, 14 days) with sertraline and citalopram (antidepressants which selectively inhibit the reuptake of 5-hydroxytryptamine (5-HT)) on the responsiveness of different 5-HT receptors to their agonists, was examined in rats and mice. Sertraline and citalopram (both at a dose 5 and 10 mg/kg) antagonized (the first one more potently) the hypothermia induced in mice by 8-OH-DPAT (a 5-HT1A agonist), but not the behavioural syndrome induced in rats by this substance. The m-chlorophenylpiperazine-induced hypothermia in mice (a 5-HT1B effect) was increased by sertraline and citalopram (only in a dose of 10 mg/kg). Both antidepressants, given repeatedly (as well acutely) attenuated exploratory hypoactivity induced in rats by m-chlorophenylpiperazine (a 5-HT1C effect). L-5-HTP-induced head twitches in mice (5-HT2 effect) were antagonized dose-dependently by both repeated sertraline and citalopram. Both antidepressants (citalopram only in higher dose) reduced the fenfluramine-induced hyperthermia in rats (5-HT2 effect). The results indicate that sertraline and citalopram given repeatedly decrease the responsiveness of 5-HT1A (presynaptic) and 5-HT2 receptors but increase the responsiveness of 5-HT1B receptors to respective agonists.
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Br J Pharmacol. 1992 Apr;105(4):863-8.
Neuroendocrine response to clonidine and 8-OH-DPAT in rats following chronic administration of desipramine or sertraline.
O'Donnell JM, Grealy M.
Department of Pharmacology, University College, Galway, Ireland.
1. Rats were administered either desipramine (DMI) or sertraline daily at doses 7.5 mg kg-1 or 10 mg kg-1, i.p., respectively and the effects on the functional state of hypothalamic neuroendocrine control mechanisms assessed by measurements of plasma hormones following acute drug challenge. The effects of treatment on gross behaviour and brain adrenoceptor density were also determined. 2. Both DMI and sertraline caused significant reduction in activity measured as ambulation and rearing at 14 days of treatment. 3. All animals were chronically cannulated after 14 days of treatment and tested for neuroendocrine response to acute i.v. clonidine (50 micrograms kg-1) or 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 250 micrograms kg-1) after 21 or more days of treatment. 4. Rats treated with DMI but not sertraline showed a virtually complete suppression of the growth hormone (GH) secretion elicited by clonidine in controls, while the secretion of corticosterone was augmented. 5. Treatment with DMI but not sertraline led to a significantly greater 8-OH-DPAT-induced secretion of prolactin than in the control rats, while the plasma concentrations of corticosterone following 8-OH-DPAT were not influenced by either DMI or sertraline treatment. 6. The density (but not the affinity) of cerebral cortical binding of [3H]-dihydroalprenolol was significantly reduced by DMI treatment. 7. These results show that DMI treatment blunted the sensitivity of post-synaptic alpha 2-adrenoceptors, accompanied by complex interactions manifested as increased responsiveness of alpha 1-adrenoceptors and 5-HT1A receptors. Sertraline had no significant neurendocrine effects at a dose which significantly reduced gross activity.
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