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Biomedical subjects

A J Friedhoff

Publications and source records attributed to A J Friedhoff.

At least 91 records · Page 5Linked to original sources
PubMed1980

Platelet monoamine oxidase as a function of nongenetic factors.

The level of platelet monoamine oxidase (MAO) has been found to be abnormally low in certain types of schizophrenia and in a number of other pathological conditions. It has been suggested that MAO in platelets may be a genetic marker for a subgroup of patients with schizophrenia; however, we have demonstrated that several nongenetic factors influence platelet MAO activity by affecting the platelet rather than the MAO enzyme protein. We have observed platelet MAO activities to be heterogeneously distributed in a given subject's platelet population, heavy platelet fractions having significantly higher specific activity than light platelet fractions. We have also found platelet MAO activity to be significantly correlated with mean platelet volume, platelet protein densities, and protein content per platelet. These changes, which might be induced by drugs and stress, could modify production, mobilization, and clearance of platelets and, hence, influence apparent MAO activity.

Antipsychotic Agents↗
PubMed1980

An un-dopamine hypothesis of schizophrenia.

The dopamine hypothesis of schizophrenia is examined critically. Although the hypothesis is couched in chemical terms, the evidence is primarily pharmacologic. In addition, neuroleptic mechanisms do not fit a simple hyperdopaminergic formulation, and treatment efficacy points to a general psychotic rather than specific schizophrenic role for dopamine. Most compromising to the hypothesis is the therapeutic action of L-dopa when combined with neuroleptics in chronic schizophrenics. Dopamine appears important but cannot be viewed as a simple pathogen.

Antipsychotic Agents↗
PubMed1979

Enduring changes in dopamine receptor cells of pups from drug administration to pregnant and nursing rats.

A decrease in specific [3H]spiroperidol binding to rat caudate tissue and a parallel decrease in sensitivity to apomorphine in eliciting stereotyped behavior was observed in the offspring of rat mothers treated with either haloperidol or alpha-methyl-p-tyrosine-methyl ester during pregnancy. In contrast, evidence of increased dopamine-receptor sensitivity was observed in the pups if haloperidol was administered to their mothers postpartum during nursing rather than during pregnancy.

Animals↗
PubMed1979

Multiple molecular forms of catechol-O-methyltransferase. Evidence for two distinct forms, and their purification and physical characterization.

Catechol-O-methyltransferase (COMT: EC 2.1.1.6) has been shown to exist in the soluble fraction of rat liver as two distinct molecular forms, designated COMT I and COMT II, which are separable by gel filtration, ion exchange chromatography, and sedimentation. The predominant form, COMT I, has a smaller Mr of about 24,000, as determined by gel filtration and sedimentation, and less negative charge, whereas the minor form, COMT II, has a larger Mr of about 47,500 and more negative charge. The COMT I and COMT II have been purified 450- and 205-fold, respectively, from rat liver by a newly developed procedure which gives homogeneous enzyme preparations with respect to catechol-methylating activities. The molecular properties of the predominant form, COMT I, were: s20,w, 2.7; D20,W, 10.5; Stokes radius, 20.1 A; f/fo, 1.08; and pI, 4.9. For the minor form, COMT II, the values were s20,w, 3.8; D20,w, 7.3; Stokes radius, 28.7 A; f/fo, 1.23; and pI, 4.8. Catechol-O-methyltransferase was found to exhibit tissue-specific isozymic patterns in the distribution of its two variant forms. In the rat tissues, the liver and kidney exhibited the presence of the two physically separable forms. Catechol-O-methyltransferase was also found as two distinct molecular forms in human tissues, including liver, brain, and placenta. The two forms of human catechol-O-methyltransferase were not distinguishable by the criteria of gel filtration from their counterparts in rat liver, indicating that the two molecular forms of human and rat liver catechol-O-methyltransferase are homologous. No interconversion of one molecular form of catechol-O-methyltransferase into the other was observed under experimental conditions employed. Available evidence indicates that the two molecular forms of catechol-O-methyltransferase are genetically dissimilar proteins.

Animals↗
PubMed1978

Paradoxical reaction to L-dopa in schizophrenic patients.

The authors administered 6 g of L-dopa to 8 schizophrenic patients and 750 mg of chlorpromazine to 7 schizophrenic patients. Chlorpromazine showed only a modest advantage over L-dopa and only on some Brief Psychiatric Rating Scale factor scores, and at maximum dosage the thought disturbance factor score in the L-dopa-treated group was not worse than at baseline. The results suggest that L-dopa is associated more with toxic than with schizophreniform symptoms and that there is adaptation to its effects. The authors discuss implications of these findings for the dopamine hypothesis of schizophrenia.

Adult↗
PubMed1978

Human platelet MAO in drug-free and medicated schizophrenic patients.

The authors compared platelet monoamine oxidase activity in drug-free chronic and acute schizophrenic patients, medicated chronic schizophrenic patients, and normal controls. A significant decrement in MAO activity was found only in medicated chronic schizophrenic patients. The possible mechanism for this finding is discussed.

Acute Disease↗
PubMed1978

The neuroleptic hypothesis: study of the covariation of extrapyramidal and therapeutic drug effects.

A therapeutic trial with chlorpromazine was conducted with a homogeneous (for age and sex) group of recently admitted schizophrenic patients. Extrapyramidal effects were measured through quantitative analysis of digital tremor, after four days of fixed-dose treatment. Assessment of treatment efficacy was based on Brief Psychiatric Rating Scale ratings, done at the end of four weeks' treatment. Those patients whose tremor was least affected by drug were most likely to benefit from the treatment. Implications of this negative correlation for our understanding of the neuroleptic hypothesis and the closely associated dopamine hypothesis of schizophrenia are discussed.

Adolescent↗
PubMed1978

In vivo formation of dopamine from 3,4-methylenedioxyphenethylamine in the rat.

Administered 1-C14-3,4-methylenedioxyphenethylamine led to the excretion of about 2% of the urinary C14 as conjugated dopamine and 3-methoxytyramine metabolites, in tranylcypromine treated rats. The amine was not excreted unchanged. The major metabolites were identified as conjugates of methylenedioxyphenylacetic acid, homovanilic acid and dihydroxyphenylacetic acid. The latter are derived by the further metabolism of conjugated methylenedioxyphenylacetic acid. Administered tranylcypromine doubled the excretion of conjugates of labeled dopamine and3-methoxytyramine. NADPH served as a cofactor for the microsomal demethylenation of the amine.

3,4-Methylenedioxyamphetamine↗
PubMed1978

A comparison of the onset of action and therapeutic efficacy of amoxapine and amitriptyline.

A total of 61 moderately to severely depressed outpatients were treated for four weeks with either amoxapine (a dibenzoxapine tricyclic) or amitriptyline. This double blind study showed that amoxapine was as effective as amitriptyline and had an earlier onset of action. Maximum doses used were 300 mg of amoxapine and 150 mg of amitriptyline. Side effects were similar for the two drugs, except for impotence or loss of libido in eight male amoxapine, as against three amitriptyline patients. Laboratory, EKG, and vital signs findings showed no pathological trends.

Adolescent↗