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Biomedical subjects

R J Baldessarini

Publications and source records attributed to R J Baldessarini.

At least 19 recordsLinked to original sources
PubMed1979

Prenatal and early postnatal beta-adrenergic receptor-mediated increase of cyclic AMP in slices of rat brain.

The levels of cyclic AMP in slices of cerebral cortex and cerebellum from newborn rats were significantly, but transiently, increased by exposure to the beta-adrenergic agonist, isoproterenol. Isobutylmethyxanthine, an inhibitor of phosphodiesterase, enhanced this effect and permitted its detection in cerebral cortex obtained from the prenatal rat. These results are consistent with the possibilities that functional noradrenergic synapses are formed early in the ontogeny of the CNS, and that norepinephrine may exert cyclic AMP-mediated influences on brain development.

1-Methyl-3-isobutylxanthine↗
PubMed1979

Methylation hypothesis.

L-Methionine had no behavioral effects in normal humans and failed to increase concentrations of S-adenosylmethionine (methyl donor) in human or rat blood, while increasing rat liver levels more than fivefold. Methionine or S-adenosylmethionine in very high doses had almost no effect on methylation of tritiated levodopa in rodent tissues; various "methyl acceptor" molecules, including nicotinamide, guanidineacetic acid, and estradiol similarly had little effect. In rabbit lung, methionine and S-adenosylmethionine not only failed to increase production of dimethyltryptamine, but actually decreased it, possibly due to end-product inhibition by S-adenosylhomocysteine, which also strongly inhibited methylation of dopa in rat. These results fail to support several predictions of the "methylation hypothesis" concerning the pathophysiology and potential treatment of idiopathic psychotic disorders and leave the consistent clinical worsening effects of methionine in schizophrenia unexplained.

Adult↗
PubMed1979

Effects of alternative transmitter amines on cyclic AMP formation in rat brain tissue.

Aromatic amines and related compounds, some of which are taken up and released from nerve terminals, might act at brain receptors ordinarily stimulated by traditional amine neurotransmitters. Several of these compounds were evaluated for their ability to stimulate or impede synthesis of cyclic AMP in rat striatal homogenates and cortical slices. In contrast to catecholamines, most had no effect, consistent with their possible role as false transmitters.

Amines↗
PubMed1979

The "neuroleptic" antipsychotic drugs. 1. Mechanisms of action.

The antipsychotic drugs have provided effective and relatively safe treatment of schizophrenia, paranoid illnesses, and manic-depressive conditions marked by psychotic features. These agents are sometimes called "neuroleptic," as virtually all produce signs of extrapyramidal neurologic disorders in addition to their antipsychotic actions; in part, evidently, the neuroleptic effects are an artifact of the means of screening of potential new agents. These agents have a strong and selective antagonistic action on synaptic mechanisms in the brain mediated by dopamine as a neurotransmitter. This antidopamine action almost certainly contributes importantly to their parkinsonism effect (basal ganglia) and their prolactin-elevating (hypothalamic) effect; in addition, antipsychotic actions may be mediated by antidopamine effects, possibly in limbic and other forebrain centers.

Animals↗
PubMed1979

The "neuroleptic" antipsychotic drugs. 2. Neurologic side effects.

The specific neurologic side effects of the antipsychotic agents include acute dystonias, parkinsonism, motor restlessness, and late choretoathetosis. Treatment of the acute reactions is usually effected by the use of anticholinergic agents; treatment of the later dyskinesias is unsatisfactory, and these reactions are to be avoided by judicious use of antipsychotic drugs for long-term treatment.

Akathisia, Drug-Induced↗
PubMed1979

Status of psychotropic drug blood level assays and other biochemical measurements in clinical practice.

Assays of drug levels in blood and of other biochemical characteristics of psychiatric patients are being proposed for clinical application, although their utility in practice remains uncertain. Exceptions are the assay of blood levels of anticonvulsants and of lithium ion. Assays of antidepressant drugs may be especially helpful in the evaluation of unexpected responses or in the avoidance of unwanted toxic effects and promise to permit more efficient predictions of individual requirements. Assays of platelet MAO activity or urinary MHPG excretion remain clinically less useful. Attempts to correlate blood levels of antipsychotic agents with clinical effects have been disappointing, although newer assay methods may prove more useful.

Anticonvulsants↗
PubMed1979

Plasma levels of apomorphine following intravenous, intraperitoneal and oral administration to mice and rats.

Clinical use of the potent dopaminergic partial-agonist apomorphine (APO) in a wide variety of neuropsychiatric disorders is hampered by a lack of data concerning tissue/plasma levels following various routes of administration. In the present experiments, plasma levels were assessed at various times up to 4 hours after APO administration IV, IP, and PO to mice and rats. Plasma levels of total radioactivity after PO administration of [3H]-APO were 50 to 65% of those seen after IV administration, but brain levels were almost undetectable after PO administration. Organic solvent-extractable concentrations of tritium-labelled material after IV and IP administration of [3H]-APO to mice were significantly lower than the levels of total radioactivity, while after PO administration, these concentrations were minimal. Similar results were observed in rats following IV and PO administration of [3H]-APO.

Administration, Oral↗
PubMed1978

Inhibition of 5,7-dihydroxytryptamine-induced supersensitivity to 5-hydroxytryptophan in mice by treatment with cycloheximide.

Intracisternal injection of 5,7-dihydroxytryptamine (5,7-DHT) following treatment with desmethylimipramine induced development of behavioral supersensitivity to the intraperitoneally administered serotonin precursor 5-hydroxytryptophan (5-HTP) in the mouse. This behavioral syndrome, characterized by tremor and muscle twitches (myoclonus), showed a clear dose-response relationship with 5,7-DHT as well as with 5-HTP. Mice lesioned with a low dose of 5,7-DHT (20 micrograms) or a placebo were treated repeatedly with a protein synthesis inhibitor, sycloheximide (45 mg/kg, s.c., every 12 h for up to 10 days). This treatment resulted in a reversible decrease of cerebral protein synthesis varying between 70 and 20% with time between treatments. The myoclonic response to 5-HTP in animals pretreated with 5,7-DHT and by cycloheximide showed a decrease in intensity within 24 h when evaluated quantitatively by an electronic activity monitor, the results of which were confirmed by direct observation. Cycloheximide also exerted a similar, though smaller, effect following full development of sensitivity to 5-HTP over 10 days. These effects may de mediated by inhibition of rapidly turning over serotonin receptor proteins, although their interpretation is somewhat obscured by possible toxic effects of cycloheximide.

5,7-Dihydroxytryptamine↗
PubMed1978

Inhibition of dopamine-stimulated adenylate cyclase activity by phenoxybenzamine.

Phenoxybenzamine at a concentration of 2 X 10(-6 M) produced half-maximal inhibition of dopamine-stimulated adenylate cyclase activity in homogenates of rat striatum. Inhibition was sharply dependent on time and temperature of preincubation with the inhibitor. When included in the preincubation medium, dopamine was nearly 8 times more effective than norepinephrine at protecting against this inhibition, whereas neither isoproterenol nor methoxamine appeared to protect at all. These results suggest a direct, and possibly irreversible, interaction of phenoxybenzamine with the dopamine-binding component of the adenylate cyclase.

Adenylyl Cyclase Inhibitors↗
PubMed1978

Activities of types A and B MAO and catechol-o-methyltransferase in blood cells and skin fibroblasts of normal and chronic schizophrenic subjects.

We assayed activities of monoamine oxidase (MAO) type B in blood platelets and type A (and B) in fibroblasts cultured from punch biopsy specimens of skin, as well as of catechol-O-methyltransferase (COMT) in erythrocytes and fibroblasts. Fibroblasts contained moderate amounts of both forms of MAO (types A and B) found in human brain and large amounts of COMT activity. Activities of both enzymes correlated poorly between fibroblasts and blood cells. Comparing carefully diagnosed chronic schizophrenics with age-matched normal young men, we found no difference in these biochemical variables, nor could we distinguish patients with paranoid symptoms. In contrast, we confirmed markedly lower MAO activities in platelet samples from chronic patients provided by colleagues at the National Institute of Mental Health. Results concerning MAO and COMT activities are now sufficiently inconsistently characteristic of schizophrenics as to question their clinical applicability and to indicate a need for further critical evaluation, with special attention to diagnosis, matching of subjects, and effects of possible spurious environmental variables.

Adolescent↗