Disease relevance of DN 1417

• Treatment of amyotrophic lateral sclerosis with the TRH analog DN-1417 [1].
• The involvement of nigrostriatal neurons in DN-1417-induced motor hyperactivity is suggested [2].
• This speculation was supported by the dose-dependent inhibition of PTZ-induced generalized seizures by the pre-treatment with TRH or its analogue DN-1417 into the cerebral ventricle [3].
• To study the role of the pituitary in mediating this action, we have evaluated the effect of TRH analogs lacking hypophysiotropic activity, acid-TRH and DN 1417, in blocking glucagon-induced hyperglycemia in mice [4].
• Following this report, we studied the efficacy and safety of DN-1417 treatment in 10 intractable epileptic children ranging in age from 6 months to 11 years (mean 4 years), including 7 with Lennox syndrome (LS), 2 with West syndrome (WS) and 1 with degenerative myoclonus epilepsy (DME) [5].

Psychiatry related information on DN 1417

• Peripheral administration of DN-1417 (0.2-20 mg/kg, i.p.) caused a significant, dose-dependent increase in total spontaneous motor activity, with a definite increase in rearing behaviour [6].
• Clinical prospects of an analog of thyrotropin-releasing hormone (DN-1417) and des-tyrosine-gamma-endorphin (DT gamma E) in schizophrenia were examined by using the Brief Psychiatric Rating Scale (BPRS) and the electroencephalogram (EEG) [7].

High impact information on DN 1417

• Lack of usefulness of DN-1417 for characterization of a CNS receptor for thyrotropin-releasing hormone [8].
• The effect of DN-1417, a thyrotropin-releasing hormone (TRH) analogue, on photosensitivity and cortically kindled seizures was examined in seven Senegalese baboons (Papio papio) [9].
• We examined the anticonvulsant effects of DN-1417 an analog of the thyrotropin-releasing hormone (TRH) in seizure-prone El mice [10].
• Clinical study of oral administration of DN-1417, a TRH analog, in patients with intractable epilepsy [11].
• The peripheral administration of DN-1417 inhibited gastrointestinal transit but MK-771 had no effect [12].

Chemical compound and disease context of DN 1417

• The lack of tolerance to motor hyperactivity, however, raises the question as to whether DN-1417-induced hyperactivity may be mediated by the activation of mesolimbic DA neurons [2].
• TRH and its analog (DN-1417) inhibited PTZ-induced generalized seizures dose-dependently [13].

Biological context of DN 1417

• These findings suggest that depolarization of the ventral root induced by TRH and DN-1417 is due to a direct action on motoneuronal membranes, and that an increase in the monosynaptic reflex is in part due to a depolarization of motoneurones [14].
• Intravenous administrations of TRH and its analog DN-1417 (gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide), which has less endocrine activity, produced a marked increase in the monosynaptic reflex (MSR) and depolarization of the ventral root, without affecting the dorsal root reflex (DRR) and the resting potential of the dorsal root [14].
• Effects of a new thyrotropin-releasing hormone analogue (DN-1417) on evoked responses and long-term potentiation in the dentate gyrus of rat [15].
• Eighty micrograms of DN-1417 injected i.c.v. reduced granule cell excitability with a small increase in the excitatory postsynaptic potential (EPSP) and reduced LTP of the EPSP [15].
• Effect of TRH and DN-1417 on the vestibulo-ocular reflex in squirrel monkeys [16].

Anatomical context of DN 1417

• DN-1417 is an analog of thyrotropin-releasing hormone, which has less endocrinologic activity, but more anterior horn cell stimulating effect (with no "autorefractory state") [1].
• Furthermore, DN-1417 (5 X 10(-5) M) significantly enhanced the spontaneous release of [3H]dopamine from the rat nucleus accumbens slices in vitro [6].
• TRH and DN-1417 were less active in cortical membranes whereas RX 77368 was some three times more active than in striatum and amygdala [17].
• The administration of DN-1417, a synthetic derivative of TRH with more potent central action, significantly reduced specific [3H]GABA binding in the cerebellum, whereas [3H]GABA binding in the cerebral cortex was not changed [18].
• GRP (10(-5) M), neurotensin (NT, 10(-5) M) and DN 1417 (10(-5) M) also stimulated spontaneous release of DA and NE from the hypothalamus [19].

Associations of DN 1417 with other chemical compounds

• A treatment trial with an analog of thyrotropin-releasing hormone (DN-1417) in schizophrenia [20].
• These findings indicate that the motor stimulatory action of DN-1417 appears to be mediated primarily via a dopaminergic mechanism by enhancing the release of dopamine from nerve terminals, including the nucleus accumbens in the mesolimbic dopamine system, and, in turn, the rearing may be mediated via noradrenergic mechanism [6].
• The administration of methyl naltrexone had little effect on loperamide-induced inhibition of gastrointestinal transit but antagonized the potentiating effect of MK-771 and DN-1417 [12].
• Atropine (0.1 mg/kg s.c.) stopped DN-1417-stimulated gastric acid secretion [21].
• Chronic DN-1417 produced no significant change in 3H-spiperone binding in the prefrontal cortex, nucleus accumbens, olfactory tubercles and striatum, while striatal 3H-DA binding displaced by 30 nM spiperone was enhanced after chronic treatment [2].

Gene context of DN 1417

• The results suggest that TRH, MK-771 and DN-1417, in behaviorally active doses, exert a marked endocrine effect on prolactin secretion in estrogen-primed rats, but not in ovariectomized rats or normal male rats [22].
• Effect of TRH analog (DN-1417) on tyrosine hydroxylase activity in mesocortical, mesolimbic and nigrostriatal dopaminergic neurons of rat brain [23].
• In the prefrontal cortex medial field, nucleus accumbens and olfactory tubercles, TH activity assayed under the suboptimal condition was not modified by DN-1417 treatment [23].
• These results suggest that GRP, NT and DN 1417 act at the hypothalamic catecholamine nerve terminals and stimulate the release of DA and NE in the rat [19].
• The present study showed that DN-1417 had a dose-dependent anticonvulsant activity on El mouse seizure [24].

Analytical, diagnostic and therapeutic context of DN 1417

• Intraperitoneal injection of DN-1417 with 150 and 450 mg/kg significantly increased the El mouse seizure threshold in a dose-dependent manner [10].
• Radioimmunoassay for an analog of thyrotrophin-releasing hormone, gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide (DN-1417) [25].
• These results suggest that the positive symptoms of schizophrenia are improved by DN-1417 treatment, and that the alterations in BPRS scores coincide with changes in the frontal EEG [7].
• The effects of a recently synthesized analogue, thyrotropin-releasing hormone (TRH) analogue, DN-1417, on evoked responses and long-term potentiation (LTP) of the perforant path input to the dentate gyrus were examined in normal rats and after hypophysectomy [15].

References