Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tiflucarbine (TVX P 4495), a new putative antidepressant drug (AD) with a chemical novel among AD's [9-ethyl-4-fluoro-1-methyl-7,8,9,10-tetrahydrothieno (3,2-e)-pyrido(4,3-b)indole lactate], a potent inhibitor of the 5-hydroxytryptamine (5-HT) uptake, was studied in rats and mice, mostly with regard to its possible effect on the noradrenaline (NA) uptake and 5-HT postsynaptic receptors. Tiflucarbine exerted no effect on the reserpine hypothermia, attenuated the apomorphine hypothermia and enhanced the TRH-induced hyperthermia. It did not prevent tryptamine convulsions or the fenfluramine-induced hyperthermia, and inhibited the L-5-hydroxytryptophan-induced head twitches (at a high dose only). It stimulated the hind limb flexor reflex preparation of the spinal rat in cyproheptadine-reversible manner. In the behavioral despair test it shortened the immobility time. Tiflucarbine administered repeatedly enhanced the D-amphetamine-induced locomotor hyperactivity and inhibited the clonidine-induced aggressiveness. The results indicate that tiflucarbine exhibits characteristics of a poor inhibitor of the NA uptake (irrespective of its strong inhibitory effect on the 5-HT uptake), and has no effect on 5-HT2 postsynaptic receptors. When used repeatedly, it enhances--like other AD--responsiveness of the central dopamine system.
 ...
PMID:Some central effects of tiflucarbine, a new potential antidepressant drug. 282 40

The ability of desipramine and maprotiline (NA uptake inhibitors), as well as citalopram and femoxetine (5-HT uptake inhibitors) to protect mice against brain NA depletion induced by H 77/77 (4-alpha-dimethyl-m-tyramine), has been compared with their ability to counteract reserpine (2.5 mg kg-1)- or apomorphine (16 mg kg-1)-induced hypothermia and to potentiate TRH (40 mg kg-1)-induced hyperthermia in mice. While both NA uptake inhibitors antagonized the action of H 77/77, maprotiline being weaker than desipramine, femoxetine and citalopram were inactive. However, in contrast to citalopram, femoxetine was active in the other tests, being about twice as weak as maprotiline, which itself was several times weaker than desipramine in those tests. On the basis of the results obtained it is concluded that functional in-vivo tests for NA uptake inhibitors are more sensitive than the H 77/77 biochemical test; moreover, femoxetine, which in-vitro studies is less selective than citalopram, may inhibit the uptake of NA in-vivo.
 ...
PMID:Biochemical and pharmacological tests for the prediction of ability of monoamine uptake blockers to inhibit the uptake of noradrenaline in-vivo: the effects of desipramine, maprotiline, femoxetine and citalopram. 289 25

Anesthesia with a large dose of pentobarbital (55 mg/kg, i.p.) caused a sustained decrease in brain temperature (Tb), which was monitored with a probe placed in the midbrain reticular formation. The administration of TRH to the lateral ventricle antagonized this hypothermia. None of the acute surgeries examined in this paper (adrenal-demedullectomy, septal knife cuts, electrolytic lesions of the hypothalamus and midbrain knife cuts) had any essential effect on this antagonism by TRH. These results suggest that centrally-administered TRH exerts its effect on thermoregulation, at least in part, through brain structure(s) caudal to the midbrain.
 ...
PMID:Antagonism by thyrotropin-releasing hormone (TRH) of pentobarbital-induced hypothermia in rats with brain lesions. 309 62

The effects of a new TRH analogue, YM-14673 (N alpha-[[S)-4-oxo-2-azetidinyl)carbonyl]-L-histidyl-L-prolinamide dihydrate) on the central nervous system were compared with those of TRH. YM-14673 was 10-40 times more potent than TRH in antagonizing pentobarbital-induced sleep and hypothermia, and ethanol-induced hypothermia in mice. YM-14673 accelerated recovery from disturbed consciousness induced by concussive head trauma in mice and normalized the behavior and spontaneous EEG disturbed by electrolytic lesion of the hypothalamus in cats with 25-100 times greater potency than that of TRH. In the tests on pentobarbital sleeping time and EEG disturbance, the cerebral activating activity of YM-14673 was 8-36 times longer-lasting than that of TRH. These results indicate that YM-14673 possesses potent arousal effects on the central nervous system. The mode of action of YM-14673 was also discussed.
 ...
PMID:Effects of a new TRH analogue, YM-14673 on the central nervous system. 312 85

Effects of YM-14673 (N alpha-[[S)-4-oxo-2-azetidinyl)-carbonyl]-L-histidyl-L-prolinamide dihydrate), a new TRH derivative, on reserpine-induced behavioural and electroencephalographic changes were observed in comparison with those of TRH. YM-14673 antagonized reserpine-induced hypothermia and decrease in convulsion threshold in mice. The number of PGO waves recorded from the lateral geniculate body was decreased by administration of YM-14673 in reserpinized cats. The anti-reserpine activity of intravenous YM-14673 was about 8-20 times more potent than that of TRH. In inhibiting reserpine-induced hypothermia, the oral ED2 degrees C relative to IV ED2 degrees C as an indirect indication of absorption rate of the drugs was 15 for both YM-14673 and TRH. These results suggest that YM-14673 possesses more potent facilitatory effects on the central monoamine systems than TRH.
 ...
PMID:Antagonizing effects of YM-14673, a new TRH derivative, on behavioral and electroencephalographic changes in reserpinized animals. 313 91

It has been observed that basal and/or TRH-stimulated serum TSH levels occasionally conflict with the actual values of circulating thyroid hormones in patients with anorexia nervosa. In the present study sixteen female patients with anorexia nervosa during self-induced starvation displayed clinical findings suggesting hypothyroidism, e.g., cold intolerance, constipation, bradycardia, hypothermia and hypercholesterolemia in association with decreased serum total T3 (62.8 +/- 5.2 ng/dl) and T4 (6.6 +/- 0.3 micrograms/dl). Markedly decreased T3 correlated positively with average heart rate (r = 0.5655, P less than 0.025) and negatively with total cholesterol (r = -0.7413, P less than 0.005). This result may suggest that peripheral metabolic state of the underweight anorexics depends considerably upon the serum T3 concentration. Despite decreased total thyroid hormones, free T4 assayed by radioimmunoassay was normal in all five cases examined (1.4 +/- 0.2 ng/dl) and the free T4 index in fifteen cases was normal except in one case. Basal TSH was not increased and TSH response to exogenous TRH was not exaggerated in any. These results may be compatible with a theory that free T4 has a dominant influence on pituitary TSH secretion. Furthermore, glucocorticoids may also have some influence on depressed TSH response, because an inverse correlation between increased plasma cortisol and the sum of net TSH increase after TRH was observed in twelve cases examined. In conclusion, it is suggested that normal sensitivity of peripheral tissues and pituitary thyrotroph to different circulating thyroid hormones is maintained in anorexia nervosa patients even during severe self-induced starvation, and that the metabolic state in these patients is considerably under the influence of circulating T3.
 ...
PMID:Assessment of the relationship between serum thyroid hormone levels and peripheral metabolism in patients with anorexia nervosa. 319 56

A potential antidepressant activity and an antiserotonin action of Org 8282, delta (13b, 4a), 4a-carba-mianserin, was studied in mice and rats. Org 8282 did not affect the reserpine-induced hypothermia, hypoactivity and ptosis, did not modify the apomorphine-induced hypothermia and the TRH-induced hyperthermia in mice, did not change the motor stimulation and stereotypy produced by amphetamine. It was inactive in the behavioral despair test in rats and mice. On the other hand, Org 8282 inhibited the head twitch reaction after 5-HTP in mice, the tryptamine-induced clonic convulsions of forepaws in rats, the hyperthermia produced by fenfluramine and m-CPP in rats kept at a high ambient temperature, and the quipazine-induced stimulation of the flexor reflex activity in the spinal rat. These results indicate that Org 8282 is inactive in tests commonly applied for assessment of antidepressant action but--like mianserin--it exerts an antiserotonin activity.
 ...
PMID:The lack of antidepressant properties and a potent central antiserotonin activity of Org 8282. 377 30

Rats made nutritionally iron-deficient (ID) have significantly diminished haemoglobin, serum iron and hypothermic response to d-amphetamine (15 mg/kg). The reduction of d-amphetamine induced hypothermia is comparatively greater in the dark than in the light period. Neither TRH (1 mg/kg) nor CG 3703, a peptidase resistant TRH analogue (1 mg/kg), induced hypothermia in control of ID animals. However, in combination with d-amphetamine, TRH and CG 3703 did not alter the hypothermic effect observed initially with d-amphetamine. In contrast to control animals, ID rats treated with saline or d-amphetamine (15 mg/kg) exhibited a greater degree of motor activity in the light as compared to the dark period. However, the overall activity (light plus dark) was unchanged in the ID group. The motor activity in response to TRH or CG 3703 was not changed as a result of iron-deficiency. These differential responses may be due to a more pronounced action of d-amphetamine on dopaminergic system, which is known to be changed in iron-deficiency, and of TRH and CG 3703 on the noradrenergic neurones.
 ...
PMID:Iron deficiency induces reversal of dopamine dependent circadian cycles: differential response to d-amphetamine and TRH. 393 24

1 The minimal dose which significantly potentiates the hyperthermia induced by thyrotrophin releasing hormone (TRH, 40 mg/kg i.p.) in mice has been established for tricyclic and other antidepressants (imipramine, amitriptyline, clomipramine, nortriptyline, maprotiline, nomifensine, viloxazine) including a specific inhibitor of noradrenaline (NA) uptake (nisoxetine). 2 The minimal effective dose in this test has been compared with the minimal dose of the same compounds antagonizing reserpine-induced hypothermia. The ratio of the two doses for each substance indicates that potentiation of TRH-induced hyperthermia is, in general, the more sensitive test. 3 A correlation seems to exist between the alpha-adrenergic effect of antidepressants and the potentiation of TRH- induced hyperthermia. Those antidepressants which do not act on alpha-adrenergic systems (butriptyline, amineptine, trazodone, danitracen, fluoxetine) are inactive in this test. 4 This property may be used to select antidepressants that activate alpha-adrenoceptor systems.
 ...
PMID:Use of potentiation of thyrotrophin releasing hormone (TRH)-induced hyperthermia as a test for screening antidepressants which activate alpha-adrenoceptor systems. 611 96

Administration of thyroliberin (TRH) to reserpinized mice causes tremor and counteracts the hypothermia in a dose-dependent fashion. The thyroliberin response is inhibited by gamma-hydroxybutyric acid (GHB) and baclofen, but not by other, more specific GABA-ergic agents, such as THIP, gamma-acetylenic GABA, and sodium valproate. Picrotoxin neither potentiates nor inhibits the thyroliberin actions. Nor are the thyroliberin effects dependent on cholinergic, monoaminergic or histaminergic mechanisms. The results repudiate a current hypothesis, that the peptide actions may be mediated by GABA-ergic pathways in the brain.
 ...
PMID:Thermic and tremorogenic effects of thyroliberin (TRH) in reserpine-treated mice--the non-involvement of GABA-ergic mechanisms. 611 36


<< Previous 1 2 3 4 5 Next >>