Search PubMed⌕ Search

Biomedical subjects

B I Diamond

Publications and source records attributed to B I Diamond.

At least 19 recordsLinked to original sources
PubMed1992

Risperidone: clinical safety and efficacy in schizophrenia.

Risperidone represents a unique pharmacology of potent antagonism of both serotonin and dopamine receptors. In a randomized, parallel-group, double-blind trial of risperidone vs. haloperidol and placebo in 36 schizophrenic patients in acute exacerbation, risperidone showed a quicker onset of antipsychotic activity than did haloperidol. Risperidone treatment was statistically superior to placebo, with a trend toward superiority to haloperidol. Risperidone did not differ from placebo on assessment scales of extrapyramidal side effects, but produced significantly less than did haloperidol. There were no major adverse reactions associated with risperidone use, but it was noted to reduce the signs of tardive dyskinesia. This study suggests that risperidone may offer a superior side-effect profile, and possibly greater efficacy, than a standard neuroleptic such as haloperidol.

Adult↗
PubMed1991

A comparative study of alpidem, a nonbenzodiazepine, and lorazepam in patients with nonpsychotic anxiety.

The use of benzodiazepines for generalized anxiety disorder (GAD) is a safe and effective treatment; however, their potential to produce dependence and impair psychomotor and cognitive functions is a drawback. In this study the efficacy and safety of alpidem, a nonbenzodiazepine, was assessed. Thirty patients who met DSM-III-R criteria for GAD were randomized to either alpidem (225 mg), lorazepam (4.5 mg), or placebo. The primary efficacy measure was the Hamilton Rating Scale for Anxiety (HAM-A). A repeated measures multivariate analysis of variance (MANOVA) was used to determine differences in HAM-A scores over time. The results showed a trend for alpidem to be more effective. Half of the alpidem group had a decrease of 50 percent or greater in their HAM-A scores with an almost equal effect on psychic and somatic symptoms. The most common side effects with alpidem and lorazepam were lightheadedness, drowsiness, and daytime tiredness. Moreover, treatment with alpidem did not manifest any withdrawal symptoms. Thus nonbenzodiazepine treatments are effective and safe for GAD.

Adult↗
PubMed1991

Does sigma receptor antagonism predict clinical antipsychotic efficacy?

The psychotogenic actions of sigma receptor agonists, such as pentazocine, have led to the hypothesis that sigma receptor antagonists may be putative antipsychotic agents. In this study, BW234U, a selective but relatively weak sigma receptor antagonist was compared at two different dosage ranges with chlorpromazine and placebo in a double-blind randomized treatment trial in schizophrenic patients undergoing acute exacerbation. During the 4-week blinded treatment period, there was a modest drop in Brief Psychiatric Rating Scale (BPRS) score in the chlorpromazine group, however, neither dosage range of BW234U, nor placebo produced a significant drop in the BPRS. Our results suggest that BW234U is an ineffective anti-psychotic agent in schizophrenics experiencing acute exacerbation of their illness. Due to BW234U's relatively weak antagonism at the sigma recognition site, this does not rule out the possibility that more potent and equally selective sigma antagonists may possess antipsychotic efficacy.

Adult↗
PubMed1978

Lithium prevention of amphetamine-induced 'manic' excitement and of reserpine-induced 'depression' in mice: possible role of 2-phenylethylamine.

Repeated treatment of mice with lithium chloride (45 mg/kg, i.p., daily for 8 days) reduced the jumping, fighting, stereotypies, and hyperactivity induced by d-amphetamine (5 mg/kg, i.p.). Lithium also reduced the hypoactivity observed 1--3 h after reserpine (0.75 mg/kg, i.p.). In biochemical studies we found that 8-day treatment with lithium markedly reduced (to 45% of control) the recovery from brain of labelled 2-phenylethylamine (PEA) following i.p. injection of labelled L-phenylalanine, while decreasing recovery from brain of labelled PEA following its i.p. injection of 63% of control. In saline-treated mice, d-amphetamine appeared to increase PEA synthesis and to accelerate its disposition, whereas reserpine enhanced PEA synthesis and reduced disposition; all of these effects were antagonized by lithium pretreatments. Since PEA appears to be one of the most powerful behavioral stimulants among endogenous neuroamines, and because its deaminated metabolites are behavioral depressants, such antagonism of brain PEA metabolism may significantly contribute to the prophylactic action of lithium against both manic and depressive behavior.

Animals↗
PubMed1978

Dopamine binding following prolonged haloperidol pretreatment.

The number of binding sites for tritiated dopamine as well as the affinity of 3H-dopamine for dopamine receptors was studied in rats chronically pretreated with the neuroleptic haloperidol. The rats were given haloperidol for 14 or 21 days and were killed on day 21. It was found that 14 days of haloperidol pretreatment followed by drug withdrawal resulted in a 67% increase in the number of 3H-dopamine binding sites in the striatum and ninefold increase in the affinity constant in the striatum. The same pretreatment regimen had no effect on either the number of receptor sites or the affinity constant in the nucleus accumbens. These results are consistent with the hypothesis that chronic neuroleptic pretreatment results in receptor site hypersensitivity in the striatum, which may be a major factor in the production of tardive dyskinesia.

Animals↗
PubMed1978

A new putative neuroregulator of the extrapyramidal system.

A putative neurotransmitter, 2-phenylethylamine, which is most highly concentrated in the extrapyramidal system of human brain, is able to reverse reserpine-induced parkinsonism in animals and elicit stereotypy. This action is only partially antagonized after catecholamine depletion by pretreatment with a-methyl-para-tyrosine, and fully blocked by pretreatment with haloperidol, a dopamine receptor blocker. Therefore, via direct and/or indirect actions, 2-phenylethylamine may serve a neuroregulatory role in the extrapyramidal system.

Animals↗
PubMed1978

Enkephalins and nigrostriatal function.

Unilateral lesions of the substantia nigra were made with 6-hydroxydopamine in rats. In this model, drugs such as naloxone, which block endogenous enkephalin receptors, potentiated agents with postsynaptic dopaminergic actions, while antagonizing agents with presynaptic dopaminergic actions. Drugs which increase brain enkephalin content (d-phenylalanine or methionine-enkephalin) antagonized postsynaptically active agents and potentiated presynaptic agents. Naloxone also reversed reserpine-induced parkinsonism in rats. Separate pre- and postsynaptic enkephalinergic neurons thus seem to modulate nigrostriatal function.

Animals↗
PubMed1978

A new animal model for schizophrenia: interactions with adrenergic mechanisms.

Amphetamine-induced stereotyped behavior in animals is proposed as a model for schizophrenia. Chronic amphetamine administration produces stereotyped behavior and a paranoid schizophreniform syndrome in man, whereas in animals a behavioral sensitization to stereotypy is evoked. We now show that phenylethylamine (PEA), an amphetamine-like stimulant concentrated in the limbic system of human brain, produces stereotypy in rats with a behavioral sensitization when chronically administered. In comparing amphetamine-induced stereotypy with PEA-induced stereotypy, we found that the alpha-adrenergic blocking agents phentolamine and phenoxybenzamine selectively antagonize PEA stereotypy, whereas the beta-adrenergic blocking agent propranolol fails to alter significantly stereotypies evoked by PEA or amphetamine administration. Catecholamine depletion by alpha-methyl-p-tyrosine administration blocks stereotypies induced by both PEA amphetamine, whereas selective norepinephrine depletion antagonizes only PEA stereotypy; the amino acid precursors of both norepinephrine and dopamine potentiate stereotypies. Therefore, PEA-elicited stereotypy, but not amphetamine-elicited stereotypy, is dependent upon norepinephrine; the significance of this for the PEA animal model of schizophrenia is discussed.

Animals↗
PubMed1978

Metabolism of an amino acid with antidepressant properties.

The amino acid D-phenylalanine exerts antidepressant properties which are believed to be due to its metabolism to brain phenylethylamine. We now show that in mice, the increase in brain phenylethylamine levels induced by L-phenylalanine, but not D-phenylalanine, is antagonized by drugs which block the stereospecific decarboxylase enzyme. Our results show that D-phenylalanine metabolism to phenylethylamine is independent of pathways involving L-phenylalanine.

Animals↗