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Biomedical subjects

R L Borison

Publications and source records attributed to R L Borison.

64 records · Page 4Linked to original sources
PubMed1976

Biochemical plasticity of synaptic transmission: a critical review of Dale's Principle.

"Dale's Principle" states that each neuron releases one and only one synaptic transmitter. Mental disorders and behavioral drug effects are attributed to activation or blockade of one or more of these specific transmitters. A series of biochemical, electrophysiological, and behavioral studies suggests the alternative view that at each monoaminergic synapse the action of the transmitter is modulated by several metabolically related substances: amine analogs (2-phenylethylamine [PEA], p-tyramine, etc.), deaminated products (aldehydes, acids, and alcohols), and possibly also amino acid precursors. In support of this view, the authors present evidence for the presence, synthesis, metabolism, and biological activity (at the cellular level, using microelectrode techniques) of amino acid, amines, and deaminated compounds metabolically related to catecholamines and sorotonin. That neuroamino acids exert direct effects (not mediated via their amine metabolites) is illustrated by the rapid effects of microiontophoretic dopa upon cortical unit activity, and by the observation that neither the lethargic effect of 5-hydroxytryptophan (considered to support Jouvet's serotonergic theory of sleep) nor the behavioral stimulant effects of dopa (considered to support the catecholamine theory of affective behavior) are significantly prevented by L-aromatic amino acid decarboxylase inhibitors. The biological activity of the deaminated metabolites of catecholamines and serotonin is illustrated by the effects of their microiontophoretic administration upon cortical units. Further, probenecid (an inhibitor of acid transport across the blood-brain barrier) is shown to qualitatively alter the effects of intraventricularly administered PEA and of its metabolite phenylacetic acid upon visual evoked potentials. Rabbit brain is shown to synthesize a series of pharmacologically active noncatecholic phenylethylamines as by-products of catecholamine metabolism. Amine modulators such as PEA differ from typical transmitters by their ability to cross biological barriers; inhibition of decarboxylase in peripheral tissues only (using alpha-methyldopa hydrazine) markedly depletes brain PEA (but not catecholamines). Because of the homeostatic control of the rate of transmitter synthesis and disposition, physiological, pharmacological, and pathological changes may be expected to affect more the tissue levels of related modulators. This modulator theory of drug action is illustrated by the effect of several psychotropic drugs upon the brain levels of PEA and of norepinephrine. For instance, amphetamine initially decreases and then increases brain PEA levels, without altering brain norepinephrine levels. The authors propose an expanded "Dale's Principle": each neuron is specific in that it releases at all its endings the same pool of chemical messengers, composed of one transmitter and metabolically related modulators, the relative proportion of which is determined by the physiological state of the cell (biochemical plasticity)...

5-Hydroxytryptophan↗
PubMedDate not supplied

Changing antipsychotic medication: guidelines on the transition to treatment with risperidone. The Consensus Study Group on Risperidone Dosing.

When treating patients with psychoses, clinicians must often consider changing their treatment from one antipsychotic agent to another. The transition may be necessary because the patient experiences serious side effects or because the existing therapy no longer controls the patient's symptoms. A principal problem in changing antipsychotic agents is the potential for withdrawal symptoms resulting from discontinuation of the existing therapy. These syndromes can manifest as reemergence or worsening of psychosis, rebound or unmasked dyskinesia, and cholinergic-rebound symptoms. Withdrawal signs and symptoms may include insomnia, nausea, vomiting, anxiety, and agitation. When switching a patient to the new antipsychotic agent risperidone, the clinician can keep withdrawal symptoms to a minimum by considering the patient's clinical history and current status. For some patients, abrupt withdrawal of the current antipsychotic may be possible. For others, the dose of the previous medication must be gradually reduced before risperidone is initiated. In many cases, the transition is best made by overlapping the existing therapy and risperidone.

Antipsychotic Agents↗
PubMedDate not supplied

Recent advances in the pharmacotherapy of schizophrenia.

The limitations of standard antipsychotics have spurred a search for novel agents that are effective against both positive and negative symptoms of schizophrenia but do not produce the extrapyramidal side effects frequently associated with the older medications. Such agents might more effectively prevent relapse, because of enhanced efficacy for the full spectrum of schizophrenic symptoms and improved tolerability--and hence greater medication compliance. Findings concerning the new antipsychotics currently available, clozapine and risperidone, are reviewed, and clozapine's usefulness as a first-line treatment is evaluated. Although serious side effects and the need for weekly blood monitoring may limit clozapine's use as a first-line treatment, risperidone appears promising in this role. Preclinical and clinical studies of new antipsychotic medications recently submitted for approval (olanzapine and sertindole) or in phase III development (quetiapine and ziprasidone) are also reviewed. The findings are encouraging, and researchers hope that some of these new agents may prove valuable as first-line treatments for schizophrenia. Pharmacoeconomic studies comparing clozapine and risperidone to the standard neuroleptics indicate that these newer drugs appear likely to lower the overall cost of treatment for schizophrenia, primarily by reducing rates of relapse and rehospitalization.

Antipsychotic Agents↗
PubMedDate not supplied

Movement disorders and new azapirone anxiolytic drugs.

Dopamine is a neurotransmitter affecting motor function, and the dopamine system is the focus of abnormality in dyskinetic diseases. An important side effect of many psychotropic drugs possessing dopamine activity is the production of movement disorders; this potential problem needs to be examined carefully with any new central nervous system drug, such as the azapirone anxiolytic drugs. The pharmacology of the azapirones, represented by the prototype, buspirone, involves several different neuroreceptor systems. Current evidence indicates that buspirone's anxiolytic activity is mediated through serotonergic mechanisms. It also displays some binding affinity for dopamine receptors, which necessitates comparisons between buspirone and neuroleptic agents in preclinical tests, clinical studies, and case reports. Although similarities occurred in some biochemical studies, neuroleptics, and not buspirone, caused an increase in dopamine receptors with chronic use. Neuroleptics typically produce this change after long-term use, which is thought to be a key factor leading to tardive dyskinesia. In standard animal behavior studies, buspirone's profile failed to match neuroleptic agents. Most notably, neuroleptics produce catalepsy; however, buspirone failed to induce catalepsy and instead reversed this effect. Isolated case reports have described buspirone as causing movement disorders, but these patients were previously exposed to neuroleptic agents. Furthermore, buspirone has been used successfully to treat anxiety in parkinsonism without exacerbating existing movement problems. In psychotropic drug use, careful patient monitoring, complete drug histories, and a full appreciation for a drug's pharmacology are necessary to decipher any likelihood of a drug relation with an adverse effect.

Aged↗