Schizophrenia h2 antagonists

The first indication that histamine might be important in the functioning of the brain was the finding that the centrally penetrating histamine H1 antagonists had marked sedative properties. Subsequently with the development of more specific compounds and drugs for the H1, H2 and H3 receptors a greater understanding of the neurotransmitter/modulator role of histamine in the CNS has been possible. Histamine is now associated with wakefulness, suppression of seizures, hypothermia and emesis. The histamine H1 antagonists have been shown to potentiate opioid-induced analgesia, and modify eating and drinking patterns as well as endocrine secretions from the pituitary gland...

Smooth pursuit eye movements (SPEM) are often abnormal in schizophrenic patients and have been proposed as a trait marker of the disorder. We explored the use of SPEM as an outcome measure in an open-label clinical trial of famotidine, an H-2 antagonist, in patients with schizophrenia; famotidine has been proposed as an adjunctive medication, particularly for negative symptoms. Prior studies using SPEM as an outcome measure have not found a significant effect with "typical" neuroleptic medication, and one study found greater SPEM dysfunction with clozapine treatment...

Recent reports suggest some utility for famotidine, a histamine type 2 (H2) antagonist, in the treatment of schizophrenia. The current report describes a treatment-resistant patient with chronic undifferentiated schizophrenia whose most dramatic symptomatic improvements were temporarily related to the open-label addition of famotidine (40-100 mg/day) to conventional neuroleptic treatment (molindone 150-200 mg/day) over the course of approximately 10 months. During one 2-week interval, his symptoms were controlled with famotidine (40 mg/day) alone...

Some patients suffering from schizophrenia fail to respond to or tolerate adequate doses of available antipsychotic medications. Thus, innovative pharmacotherapeutic approaches, such as augmentation strategies, play an important role in the management of these treatment-resistant patients. A recent case report suggested that the administration of famotidine to a patient suffering from schizophrenia with peptic ulcer disease was associated with improvement in the deficit symptoms of schizophrenia. Famotidine is a potent highly selective H2 receptor antagonist which crosses the blood-brain barrier...

There is considerable interest in the role of serotonin (5-HT) in the pathophysiology of schizophrenia and in the mechanism of action of clozapine, an atypical antipsychotic agent and a potent dopamine (DA), 5-HT2/5-HT1C and histamine (H) antagonist. Cimetidine, an H2 antagonist, produces robust, transient increase in plasma prolactin (PRL) levels in man following intravenous administration. This effect has been attributed, in part, to indirect central serotonergic mechanisms involving 5-HT2 receptors in the hypothalamus, but the evidence is inconclusive...

The non-competitive NMDA antagonist ketamine, given to schizophrenic individuals in subanesthetic doses, produced a short-lived, discrete activation of their psychotic symptoms, which had striking similarities to symptoms of their usual psychotic episodes. To further study this psychotomimetic property of ketamine, we administered 0.3 mg kg-1 of the drug to schizophrenic individuals during a [15O] water cerebral blood flow study. Regional cerebral blood flow (rCBF) was measured using H2(15)O and positron emission tomography (PET) before and after ketamine administration to identify regions of flow change, rCBF was increased in anterior cingulate cortex and was reduced in the hippocampus and primary visual cortex (lingual and fusiform gyri)...

Involvement of histamine H1 receptor in the brains of schizophrenic patients was investigated using 3H-mepyramine as a ligand. The specific 3H-mepyramine binding in the frontal cortex was saturable with the dissociation constant (Kd) of about 0.6 nM and the maximum number of binding sites (Bmax) of 64 fmol/mg protein. Specific H1 antagonists, mepyramine (Ki = 1.4 nM), promethazine (Ki = 1.4 nM), diphenylpyraline (Ki = 4.1 nM), triprolidine (Ki = 5.3 nM), diphenylhydramine (Ki = 35 nM), but not the specific H2 antagonist, cimetidine (Ki greater than 10(5) nM), strongly inhibited the 3H-mepyramine binding...