Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Haloperidol (HPD: 0.4 mg/kg, sc) completely abolished not only the ambulatory stimulation by methamphetamine (MAP: 2 mg/kg, sc) but also the induction and expression of MAP sensitization in the combined administration schedule. HPD also significantly reduced the induction of MAP sensitization when the mice were treated with HPD at 1/12, 1/4, 1, 2, 3, 4 or 5 hr but not at 1/2 hr or later than 6 hr, after each administration of MAP. The inhibition by the 3-hr post-treatment with HPD was as strong as that by the combined administration. On the other hand, a restraint of abulation for 3 hr (putting the mouse in a small jar) significantly inhibited the induction of MAP sensitization when it was started at 0/4 hr, but not at 1/2-6 hr, after each MAP administration. The inhibitory effects of restraint, starting at 0-1/4 hr, were almost equivalent to those of the post-treatments with HPD at the same times. The post treatments with HPD + restraint showed similar inhibitory effects on MAP sensitization to those of HPD alone. The repeated administration of saline together with post-treatment with either HPD, restraint or HPD + restraint did not change MAP sensitivity. These results suggest that a couple of free movement in the activity cage and stimulation of dopamine receptors for longer than 1/2 hr immediately after administration of MAP, and an agonistic effect on dopamine receptors during 1-5 hr after MAP are responsible for perfect induction of the MAP sensitization in terms of ambulation in mice.
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PMID:Haloperidol and restraint differently inhibit the induction of sensitization to the ambulation-increasing effect of methamphetamine in mice. 758 19

Haloperidol (HPD: 0.0063, 0.025, 0.1 and 0.4 mg/kg, s.c.) reduced dose-dependently the ambulation-increasing effect of methamphetamine (MAP: 2 mg/kg, s.c.) in mice. The repeated administration of MAP elicited a sensitization to its ambulation-increasing effect, and the development of sensitization was inhibited when MAP was administered in combination with HPD in the repeated administration schedule. However, any dose of HPD could not ameliorate the established MAP sensitization. Whereas, the mice experienced the repeated treatment with HPD 0.4 mg/kg showed an increase in the MAP sensitivity. The present results suggest that HPD, at comparatively higher doses, produces a denervation supersensitivity of postsynaptic dopamine receptors, and shows protective action on the development of MAP sensitization. However, it is also suggested that the established MAP sensitization is irreversible even after the treatment with HPD.
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PMID:Effects of haloperidol on the methamphetamine sensitization: assessment by ambulatory activity in mice. 830 85

1. The atypical antipsychotic profile of (R)-(+)-2-amino-4-(4-fluorophenyl)-5-[1-[4-(4-fluorophenyl)-4-oxobutyl] pyrrolidin-3-yl] thiazole (NRA0045), a potent dopamine D4 and 5-hydroxytryptamine (5-HT)2A receptor antagonist, was examined in rats. 2. Spontaneous locomotor activity was decreased dose-dependently with i.p. administration of clozapine (ED50 3.7 mg kg-1), haloperidol (ED50 0.1 mg kg-1) and chlorpromazine (ED50 0.9 mg kg-1), whereas inhibition of this type of behaviour induced by i.p. administration of NRA0045, at doses up to 10 mg kg-1, did not exceed 50%. 3. Locomotor hyperactivity induced by methamphetamine (MAP, 2 mg kg-1, i.p.) in rats (a model of antipsychotic activity) was dose-dependently antagonized by NRA0045 (ED50 0.4 mg kg-1, i.p., and 0.3 mg kg-1, p.o., respectively), clozapine (ED50 0.3 mg kg-1, i.p. and 0.8 mg kg-1, p.o., respectively), haloperidol (ED50 0.02 mg kg-1, i.p. and 0.1 mg kg-1, p.o., respectively), chlorpromazine (ED50 0.3 mg kg-1, i.p. and 3.3 mg kg-1, p.o., respectively). In contrast, the MAP (3 mg kg-1, i.v.)-induced stereotyped behaviour in rats (a model of extrapyramidal symptoms) was not affected by NRA0045 or clozapine, at the highest dose given (30 mg kg-1, i.p.). Haloperidol (ED50 0.3 mg kg-1, i.p.) and chlorpromazine (ED50 4.8 mg kg-1, i.p.) strongly blocked the MAP-induced stereotyped behaviour. NRA0045 and clozapine selectively blocked behaviour associated with activation of the mesolimbic/mesocortical dopamine neurones rather than nigrostriatal dopamine neurones. 4. Extracellular single-unit recording studies demonstrated that MAP (1 mg kg-1, i.v.) decreased the firing rate in the substantia nigra (A9) and ventral tegmental area (A10) dopamine neurones in anaesthetized rats. NRA0045 completely reversed the inhibitory effects of MAP on A10 dopamine neurones (ED50 0.1 mg kg-1, i.v.), whereas the inhibitory effects of MAP on A9 dopamine neurones were not affected by NRA0045, in doses up to 1 mg kg-1 (i.v.). Clozapine completely reversed the inhibitory effects of MAP on A10 dopamine neurones (ED50 1.9 mg kg-1, i.v.) and on A9 dopamine neurones (ED50 2.5 mg kg-1, i.v.). Haloperidol completely reversed the inhibitory effects of MAP on A10 (ED50 0.03 mg kg-1, i.v.) and on A9 dopamine neurones (0.02 mg kg-1, i.v.). NRA0045, like clozapine, was more potent in reversing the effects of MAP on A10 than A9 dopamine neurones. 5. Prepulse inhibition (PPI) is impaired markedly in humans with schizophrenia. The disruption of PPI in rats by apomorphine (0.5 mg kg-1, s.c.) was reversed significantly by NRA0045 (3 mg kg-1, i.p.), clozapine (3 mg kg-1, i.p.) and haloperidol (0.3 mg kg-1, i.p.). 6. Phencyclidine (PCP) elicits predominantly psychotic symptoms in normal humans and in schizophrenics. NRA0045 (0.03-0.3 mg kg-1, i.p.) and clozapine (0.1-1 mg kg-1, i.p.) significantly and dose-dependently shortened the PCP(1.25 mg kg-1, i.p.)-induced prolonged swimming latency in rats in a water maze task, whereas haloperidol (0.01-0.1 mg kg-1, i.p.) did not significantly alter swimming latency. 7. These findings suggest that NRA0045 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics.
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PMID:The atypical antipsychotic profile of NRA0045, a novel dopamine D4 and 5-hydroxytryptamine2A receptor antagonist, in rats. 917 95