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Biomedical subjects

A J Friedhoff

Publications and source records attributed to A J Friedhoff.

At least 73 records · Page 4Linked to original sources
PubMed1984

Receptor binding profile of tibalosine, a new antihypertensive.

The ability of 1-(2,3-dihydro-5-benzo[b]thienyl]-2-(4-phenylbutylamino)-1- propanol-(erythro) (tibalosine, CP 804 S), a new antihypertensive agent, to interact with 11 different receptors has been studied by binding assays. Tibalosine interacts specifically with alpha- and beta-adrenergic receptors and calcium channel binding sites. Ki values (nmol/l) for inhibition of specific binding are 26, 1000, 1000 and 770 respectively for the alpha 1-adrenergic, beta 1- and beta 2-adrenergic receptors and calcium channel binding sites. The interaction with adrenergic receptors is stereoselective since CP 804 S/T, the threo derivative of tibalosine, exhibits Ki values 8 to 10 times higher than those of tibalosine. The selectivity ratio between alpha 1- and alpha 2-adrenergic receptors is about 400. Tibalosine and CP 804 S/T interact with the low affinity binding sites labelled by 3H-WB 4101 in rat brain membranes. These binding sites for putative Ca2+ channel inhibitors are present in rat heart membranes and have the same characteristics as those in rat brain membranes. These results are discussed in relation with the mechanism of tibalosine antihypertensive effect.

Animals↗
PubMed1983

Induction of oral dyskinesias in naive rats by D1 stimulation.

Repetitious opening and closing of the mouth and high frequency clonic jaw movements were observed in rats challenged with dopamine agonists after acute treatment with sulpiride or a low dose of spiroperidol. SKF 38393, a specific D1 receptor agonist, alone, also induced these behaviors and cis-flupenthixol blocked them, evidence suggesting D1 dopamine receptor mediation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1983

A strategy for developing novel drugs for the treatment of schizophrenia.

Antipsychotic drugs currently in use have been developed as antidopaminergic agents; that is, normalization of psychotic symptoms occurs through a reduction in dopaminergic activity, usually by blockade of postsynaptic dopamine receptors. Based on this current understanding of the mechanism of action of antipsychotic drugs, it is suggested that one physiological role of the dopaminergic system is to down-regulate in the face of biological or psychological insult, as a means of maintaining mental stability. An attempt to develop new drugs to improve the efficiency of this down-regulative system as an alternative to conventional drugs that block dopamine receptors is proposed.

Antipsychotic Agents↗
PubMed1983

Onset of action of amoxapine and doxepin in outpatients with "mixed anxiety/depression".

In a parallel-group double-blind study, 142 outpatients with "mixed anxiety/depression" were treated with amoxapine or doxepin for 4 weeks in mean maximum daily dosages of 260 mg and 130 mg, respectively. Patients in both groups improved significantly during treatment as shown by changes in the Hamilton, Zung, Patient Self-Evaluation, and Clinical Global Impressions scales. From 24 to 31 of the 71 subjects receiving amoxapine and 16 to 24 of the 71 receiving doxepin were rated as "unquestionably improved" at the end of the treatment period on these scales. The time to achieve this degree of response was significantly shorter with amoxapine on both the CGI (p = .018) and Hamilton (p = .005) scales. Side effects were roughly comparable with two exceptions: doxepin-treated patients experienced more daytime drowsiness (p less than or equal to .05) and amoxapine-treated patients experienced more constipation (p less than or equal to .01).

Adult↗
PubMed1982

Factors contributing to the up regulation of dopaminergic receptors by chronic haloperidol.

The relationship of the magnitude and persistence of elevated striatal dopamine receptor binding sites to the dose and duration of haloperidol treatment has been examined in rats. The magnitude of elevation was found to be significantly related both to dose and duration of dose. The persistence of statistically significant receptor binding elevation, after withdrawal, was estimated to be 0.67 days/day on haloperidol. Receptor binding was carried out with 3H-spiroperidol.

Animals↗
PubMed1982

Chronic haloperidol does not increase specific dopamine receptor binding in rat frontal cortex.

The specific D2 dopamine receptor antagonist sulpiride was used to quantitate the minor component of [3H]spiroperidol binding (at 0.1 nM) to dopamine receptors in rat frontal cortex. Chronic treatment of rats with haloperidol, 0.5 mg/kg for 3 weeks or 2.5 mg/kg for 5 weeks, did not alter the specific binding of [3H]spiroperidol to dopamine receptors in frontal cortex, whereas both treatments significantly increased binding to striatal dopamine receptors. These findings may be relevant to previous studies demonstrating that the frontal cortex, but not the striatum, is resistant to the development of tolerance to the dopamine metabolite-elevating effects of chronic neuroleptic treatment.

Animals↗
PubMed1980

Radioimmunoassay measurement of creatine kinase BB in the serum of schizophrenic patients.

Brain type creatine kinase (BB) isoenzyme was measured using a highly sensitive and specific radioimmunoassay procedure (limit of detection, 1 microgram/l of sample) in two schizophrenic populations, an acute non-medicated group consisting of 35 subjects and a chronic group of 15 subjects. Since the assay can also measure the B subunit of MB isoenzyme, patients were selected so as to exclude subjects with possible heart, kidney or other ailments which might result in an increased serum creatine kinase B subunit. Both the acute schizophrenics (3.0 +/- 0.23) mean S.E.M. and the chronic schizophrenics (2.9 +/- 0.33) had serum levels of creating kinase BB similar to those of controls (2.8 +/- 0.21) and non-cardiac patients (3.5 +/- 0.58). Patients having myocardial infarction or neurovascular surgery had elevated creatine kinase B subunit. Similar but much less sensitive quantitative results were obtained using agarose multizonal electrophoresis. Despite a recent report that human brain contains the creatine kinase MM isoenzyme, analysis of five human brains using DEAE-Sephadex-A50 for MM isoenzyme fractionation, followed by immunodiffusion analysis of concentrated eluate revealed no detectable MM isoenzyme. The results from these studies suggest that the elevated serum creatine kinase activity of schizophrenic patients is most likely not of brain origin.

Animals↗