USE OF POTENTIATION OF THYROTROPHIN RELEASING HORMONE (TRH)‐INDUCED HYPERTHERMIA AS a TEST FOR SCREENING ANTIDEPRESSANTS WHICH ACTIVATE Α‐ADRENOCEPTOR SYSTEMS

Desiles, Marguerite; Rips, Richard

doi:10.1111/j.1476-5381.1981.tb09957.x

Cited by 16 publications

(9 citation statements)

References 17 publications

(18 reference statements)

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“…Since norzimelidine inhibits the uptake of 5-HT in a more potent way than zimelidine (see introduction), it could be speculated that the difference in their pharmacological action reflects simply this fact. However, some 5-HT uptake inhibitors which are more potent than norzimelidine and highly specific such as citalopram, fluoxetine and fluvoxamine (Hyttel 1982; Hyttel unpublished results on fluvoxamine), neither antagonize the hypothermia induced by reserpine or apomorphine (1-16 mg kg-l) nor potentiate TRHinduced hyperthermia (Claassen et a1 1977;Slater et a1 1979;Desiles & Rips 1981;Maj et all983;Pawbwski & Kwiatek 1983a, b;Pawlowski 1984; Table 1). Conversely, potent and highly selective NA uptake inhibitors, such as desipramine, maprotiline, oxaprotiline and talsupram (Hyttel 1982), are active in all the three tests in doses much lower than those used for norzimelidine in the present study (Slater et a1 1979;Desiles & Rips 1981;Puech et a1 1981;Maj et al 1983;Pawlowski & Kwiatek 1983a, b;Pawlowski et al 1983;Przegalinski et a1 1983;Pawlowski 1984;Pawlowski unpublished).…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, to estimate the effect of zimelidine and norzimelidine on the uptake of NA in-vivo, we have used three pharmacological tests for NA uptake inhibitors which, in our opinion, are sensitive (and specific) enough to detect even negligible NA uptake-inhibiting properties of a compound. These tests were: antagonism to reserpineinduced hypothermia in mice (Slater et al 1979;Maj et a1 1982bMaj et a1 , 1983Przegalinski et a1 1983), antagonism to apomorphine (16 mg kg-*)-induced hypothermia in mice (Puech et a1 1981;Pawkowski 1984) and potentiation of thyrotropin releasing hormone (TRH)-induced hyperthermia in mice (Desiles & Rips 1981;Pawiowski & Kwiatek 1983a, b).…”

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confidence: 99%

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Norzimelidine, a metabolite of a highly selective 5-hydroxytryptamine uptake inhibitor, can inhibit the uptake of noradrenaline in-vivo

Pawłowski

Mazela

1984

Journal of Pharmacy and Pharmacology

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Zimelidine and norzimelidine were tested for their ability to counteract reserpine (2.5 mg kg-1)- or apomorphine (1-16 mg kg-1)-induced hypothermia and to potentiate TRH (40 mg kg-1)-induced hyperthermia in mice. Norzimelidine produced positive results in all three tests, behaving like a weak NA uptake inhibitor. Zimelidine was practically inactive. We conclude that the weak inhibitory effect of norzimelidine on the uptake of NA (in-vitro experiments) may be of importance for its pharmacological action and for the clinical action of zimelidine.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Norzimelidine, a metabolite of a highly selective 5-hydroxytryptamine uptake inhibitor, can inhibit the uptake of noradrenaline in-vivo

Pawłowski

Mazela

1984

Journal of Pharmacy and Pharmacology

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“…However, this does not reflect its antidepressant properties or dopamine antagonism (Pawlowski & Mazela 1986). Maprotiline also potentiates hyperthermia induced by thyrotropin-releasing hormone and a correlation exists between the a2-adrenergic effect of antidepressants and the potentiation of thyrotropin-releasing hormone-induced hypothermia (Desiles & Rips 1981). It has been demonstrated that a1-and P-adrenoceptors are involved in the antagonistic action of maprotiline (Pawlowski & Mazela 1986).…”

Section: Discussionmentioning

confidence: 99%

Acute Toxicity Profile of Maprotiline in the Rat

D’Arcy

Dredge

Kellehir

et al. 1999

Pharmacology & Toxicology

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Abstract:The aim of the present study was to examine the toxic effects of single oral administrations of the antidepressant maprotiline at 150 mg/kg or 300 mg/kg using female Sprague-Dawley rats. Body-weight gain was significantly reduced in the group receiving 300 mg/kg on days 1-5 of the study (P<0.01). A significant reduction in food and water intake was observed on days 1 and 2 of the study (P<0.01) in the 300 mg/kg group and on day 1 in the 150 mg/kg group (P<0.05). There was a significant decrease in nocturnal home cage activity over the first five days of the study in the 300 mg/kg group (P<0.01). A significant hypothermic response was observed in both 150 and 300 mg/kg groups at 1, 2 and 4 hr after dosing (P<0.01). that had returned to control values within 8 hr following administration. This study demonstrates that a multi-parameter approach is appropriate for the investigation of high doses of antidepressants in rodents.Acute toxicity testing is of the utmost importance in the preclinical assessment of novel compounds. Traditionally, the acute toxicity of a compound was determined by means of the median lethal dose (LD50) test first described by Trevan (1927). This procedure has since been criticised on ethical grounds and there has been a search for more appropriate tests for acute toxicity in laboratory animals (Zbinden & Flury-Roversi 1981;Tattersall 1982). For instance, the "Fixed Dose" procedure ( Van den Heuvel et al. 1987) and the "Up-and-Down'' test (Bruce 1985(Bruce & 1987 have been developed, validated and have finally attained acceptance by scientific and regulatory authorities such as the Organisation for Economic Cooperation and Development (OECD), see table 1.The Fixed Dose procedure is designed to supply the data needed for classification or labelling purposes and is a three-step procedure (Van den Heuvel et al. 1987). Five rats per sex are given a 50 mg/kg oral dose of the test substance. If survival is less than 90%, a second group of animals is given 5 mglkg. If survival is again less than 900/, the substance is classified as "very toxic"; otherwise it is classified as "toxic". If there is 90% survival after the 50 mg/kg dose but with evident toxicity, the substance is classified as "harmful". If there is no evident toxicity after the 50 mg/kg dose another group of animals is given a 500 mg/kg dose. If there is no evident toxicity and 90% survival following this dose, the substance is classified as "unclassified" or "slightly toxic" (Gad & Chengelis 1998).To determine an acute toxic dose with the Up-and-down procedure female or male rats are used. Rats are dosed one at a time, starting the first animal at the best estimate of the LDS0. If the first animal is alive at the end of 24 hr, the Author for correspondence: Philip Darcy, Department of Pharmacology, National University of Ireland, Galway, Ireland (fax 353 91 525300. e-mail pipdarcy@hotmail.com).next animal is given a higher dose. If the first animal dies, then the next animal receives a lower dose. The dose for the next animal...

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“…injection of TRH had no effect on rectal temperature (Boschi & Rips,198 lb). Peripheral injection of TRH induced hyperthermia which was potentiated by a-adrenoceptor agonists and inhibited by a-adrenoceptor antagonists (Desiles & Rips, 1981). Noradrenaline (NA) given intraperitoneally (i.p.)…”

Section: Introductionmentioning

confidence: 99%

Thyrotropin releasing hormone‐induced hyperthermia in mice: possible involvement of adrenal and pituitary glands

Boschi

Nomoto

Rips

1983

British J Pharmacology

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1To investigate the hyperthermic effect of thyrotropin releasing hormone (TRH) and its potentiation by exogenous catecholamines (CA), the role of the adrenal medulla and of the pituitary gland was studied in unoperated, adrenal-demedullated or hypophysectomized mice. 2 In unoperated mice, TRH 40 mg kg-l i.p. produced a hyperthermia which was accompanied by an increase in plasma noradrenaline (NA) and adrenaline (Ad). NA or Ad, both at a dose of 1 mg kg-I i.p., enhanced the TRH-induced hyperthermia.3 Adrenal demedullation suppressed the hyperthermia and the increase of plasma CA produced by TRH but not the potentiation of this hyperthermia by exogenous CA. 4 Hypophysectomy abolished the TRH-induced hyperthermia but not the increase of plasma CA or the potentiation of this hyperthermia by exogenous CA. 5These results suggest that, in mice, both the adrenal medulla and the pituitary gland play an essential role in TRH-induced hyperthermia but not in its potentiation.

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USE OF POTENTIATION OF THYROTROPHIN RELEASING HORMONE (TRH)‐INDUCED HYPERTHERMIA AS a TEST FOR SCREENING ANTIDEPRESSANTS WHICH ACTIVATE Α‐ADRENOCEPTOR SYSTEMS

Cited by 16 publications

References 17 publications

Norzimelidine, a metabolite of a highly selective 5-hydroxytryptamine uptake inhibitor, can inhibit the uptake of noradrenaline in-vivo

Norzimelidine, a metabolite of a highly selective 5-hydroxytryptamine uptake inhibitor, can inhibit the uptake of noradrenaline in-vivo

Acute Toxicity Profile of Maprotiline in the Rat

Thyrotropin releasing hormone‐induced hyperthermia in mice: possible involvement of adrenal and pituitary glands

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