Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have indicated a noradrenergic modulation of midbrain dopamine cell activity. The effects of systemic administration of the alpha 1-adrenoceptor antagonist prazosin and the alpha 2-antagonist idazoxan on midbrain dopamine cell firing were now studied with extracellular recording from single dopamine neurons in the ventral tegmental area of chloral hydrate-anaesthetized male rats. Prazosin (0.15-0.6 mg/kg i.v.) dose dependently decreased burst firing and regularized the firing pattern of dopamine neurons, while the firing rate was unaffected. The prazosin-induced effects were abolished by pretreatment with reserpine. Idazoxan (0.5-2.0 mg/kg i.v.) increased firing rate and burst firing and made the firing pattern less regular, probably by increasing adrenergic transmission via blockade of presynaptic alpha 2-adrenoceptors. The effects of idazoxan were blocked by prazosin. The present results indicate that noradrenergic neurons modulate the dopamine cell firing pattern via excitatory postsynaptic alpha 1-adrenoceptors. This mechanism might be involved in the pathogenesis and pharmacological treatment of schizophrenia.
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PMID:Prazosin modulates the firing pattern of dopamine neurons in rat ventral tegmental area. 809 62

Idazoxan, a selective alpha 2-adrenergic antagonist, was added to stable doses of fluphenazine treatment in six patients with schizophrenia who participated in a double-blind, placebo-controlled pharmacologic study. Compared with fluphenazine alone, combining idazoxan (mean dose, 120 mg/day) with fluphenazine (mean dose, 28 mg/day) resulted in a significant decrease in Brief Psychiatric Rating Scale total symptoms (p < 0.05). Symptom ratings returned to baseline upon idazoxan discontinuation. No significant effects of idazoxan were observed on fluphenazine levels in plasma or on extrapyramidal symptoms. These pilot data are compatible with the notion that increased noradrenergic neurotransmission may enhance the therapeutic effects of typical neuroleptics in schizophrenia.
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PMID:Idazoxan, an alpha 2 antagonist, augments fluphenazine in schizophrenic patients: a pilot study. 810

Clozapine exerts superior clinical efficacy and markedly enhances cortical dopamine output compared with classical antipsychotic drugs. Here the alpha2 adrenoceptor antagonist idazoxan was administered to rats alone or in combination with the D2/3 dopamine receptor antagonist raclopride. Dopamine efflux in the medial prefrontal cortex and conditioned avoidance responding were analyzed. Idazoxan selectively potentiated the cortical output of dopamine and augmented the suppression of conditioned avoidance responding induced by raclopride. These results challenge basic assumptions underlying the dopamine hypothesis of schizophrenia and provide insight into clozapine's mode of action.
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PMID:Enhanced cortical dopamine output and antipsychotic-like effects of raclopride by alpha2 adrenoceptor blockade. 1050 54

Based on phenomenological similarities between anhedonia (reward deficits) associated with drug withdrawal and the negative symptoms of schizophrenia, we showed previously that the atypical antipsychotic clozapine attenuated reward deficits associated with psychostimulant withdrawal. Antagonism of alpha(2) adrenergic and 5-HT(2A) receptors may contribute to these effects of clozapine. We investigated here whether blockade of alpha(2) or 5-HT(2A) receptors by idazoxan and M100907, respectively, would reverse anhedonic aspects of psychostimulant withdrawal. Idazoxan treatment facilitated recovery from spontaneous nicotine, but not amphetamine, withdrawal by attenuating reward deficits and increase the number of somatic signs. Thus, alpha(2) adrenoceptor blockade may have beneficial effects against nicotine withdrawal and may be involved in the effects of clozapine previously observed. M100907 worsened the anhedonia associated with nicotine and amphetamine withdrawal, suggesting that monotherapy with M100907 may exacerbate the expression of the negative symptoms of schizophrenia or nicotine withdrawal symptoms in people, including schizophrenia patients, attempting to quit smoking.
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PMID:The alpha2 adrenergic receptor antagonist idazoxan, but not the serotonin-2A receptor antagonist M100907, partially attenuated reward deficits associated with nicotine, but not amphetamine, withdrawal in rats. 2062 63