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Biomedical subjects

E Richelson

Publications and source records attributed to E Richelson.

At least 199 records · Page 11Linked to original sources
PubMed1980

High affinity binding of tricyclic antidepressants to histamine H1-receptors: fact and artifact.

Six tricyclic antidepressants were tested for their ability to inhibit the binding of the histamine H1-receptor antagonist [3H]pyrilamine to membrane fractions from whole rat brain. Calculated inhibition constants (Ki) for the antidepressants were in the range of 2.6 x 10(-11) to 2.3 x 10(-7) M and correlated very well with their equilibrium dissociation constants derived from biological assays of the H1-receptor. Increasing the concentration of receptors present in the binding assay resulted in an overestimation of the calculated Ki's for doxepin, amitriptyline, and nortriptyline, but not for the lower affinity compounds of the series, imipramine, protriptyline, and desipramine. These results indicate: (1) the importance of receptor concentration in determining the potency of compounds which competitively inhibit, with very high affinity, the binding of a radioactively labeled ligand; (2) the need to correlate binding data with biological data.

Animals↗
PubMed1980

Involvement of calcium channels in short-term desensitization of muscarinic receptor-mediated cyclic GMP formation in mouse neuroblastoma cells.

Incubation of mouse neuroblastoma cells (clone N1E-115) with Mn2+ resulted in a rapid and transient increase in cyclic GMP formation. This effect appears to be due to an increase in calcium influx because it did not occur in the absence of extracellular calcium or in the presence of verapamil, a calcium transport inhibitor. In addition, Mn2+ inhibited muscarinic receptor-mediated cyclic GMP responses. The ability of Mn2+ to increase cyclic GMP levels was markedly diminished in cells desensitized to the effects of carbamoylcholine, suggesting that this densensitization involves inactivation of calcium entry.

Animals↗
PubMed1980

Regulation of muscarinic receptor-mediated cyclic GMP synthesis by cultured mouse neuroblastoma cells.

Mouse neuroblastoma clone N1E-115 has muscarinic acetylcholine receptors that mediate cyclic GMP synthesis. This receptor-mediated response is not significantly higher than background until the cells have been maintained in the stationary phase for at least 1 week. The basis of the influence of time in culture on the cyclic GMP response was investigated. The relative amount of cyclic GMP synthesized by intact cells was measured by radioactively labeling the GTP pool with [3H]guanine, incubating cells with agonists, and then chromatographically isolating [3H]cyclic GMP. Carbamylcholine-, ionophore X-537A-, and sodium azide-induced cyclic GMP formation increased with time in culture to a maximum of 13-, 9-, and 2.5-fold above basal, respectively. There was no change in the number or the apparent affinity of the muscarinic receptors as measured by [3H]quinuclidinyl benzylate ([3H]QNB) binding. In addition, there was no change in the apparent affinity of the receptors for agonist as measured by the ability of carbamylcholine to displace the specific binding of [3H]QNB. Guanylate cyclase activity per milligram protein and per cell increased six- and sevenfold, respectively, from day 0 to day 22. However, this increase in guanylate cyclase appeared to precede the marked increase in sensitivity of the cells to agonists. These data suggest that, in addition to guanylate cyclase and muscarinic receptors, there is another factor which is responsible for the development of this muscarinic receptor-mediated response.

Animals↗
PubMed1979

Tricyclic antidepressants: potent blockade of histamine H1 receptors of guinea pig ileum.

Six tricyclic antidepressants were tested for their ability to antagonize histamine actions at histamine H1 receptors in a bioassay for these receptors (histamine-induced contractions of guinea pig ileum). All compounds were competitive antagonists with equilibrium dissociation constants in the range of 5.6 x 10(-11) M to 1.5 x 10(-7) M. Doxepin hydrochloride and amitriptyline hydrochloride were the most potent compounds of the series and may be the most potent antihistamines known. Antagonism at histamine H1 receptors by these compounds may explain their sedative effects.

Animals↗
PubMed1979

Hallucinogens antagonize histamine H1 receptors of cultured mouse neuroblastoma cells.

Hallucinogens were competitive antagonists of histamine at the H1-receptor of cultured mouse neuroblastoma cells. Their rank order of potency at this receptor was similar to that for their potency at eliciting subjective effects in vivo. Comparison with studies of other receptors, however, suggests that no single model of drug--receptor interaction adequately accounts for the known subjective effects of these compounds.

Animals↗
PubMed1979

Neurotransmitter synthesis, storage and release by aggregating cell cultures of rat brain.

Rotation-mediated aggregating cell cultures of mechanically dissociated fetal (15-16 days gestation) rat brains between 25 and 35 days in vitro were examined for their ability to synthesize neurotransmitters and putative neurotransmitters from radioactively labeled precursors added to the culture medium. Cultures derived from whole brain synthesized [3H]acetylcholine from [3H]choline, [3H]gamma-aminobutyric acid from L-[3H]glutamic acid, [3H]dopamine from L-[3H]tyrosine, [3H]dopamine and [3H]norepinephrine from L-[3H]dihydroxyphenylalanine, and [3H]serotonin from L-[3H]tryptophan. Veratridine increased and tetrodotoxin decreased the rate of [3H]-dopamine synthesized by aggregates derived from midbrain plus hindbrain. In chase experiments in which aggregates were incubated for 4 h with radioactively labeled precursors and then for 4 h with non-radioactively labeled precursors, addition of veratridine (50 micronM) during the second 4 h incubation significantly decreased the amounts of radioactively labeled acetylcholine, L-glutamic acid, dopamine and serotonin recovered from aggregates. Tetrodotoxin (5 micronM) present during the chase significantly increased the amounts of [3H]acetylcholine and [3H]dopamine recovered from the aggregates. In addition, reserpine (4 micronM) markedly depleted [3H]dopamine from aggregates in these experiments. These results indicate that these cultured cells synthesized neurotransmitters and in addition suggest that some of these compounds are stored by and released from electrically active cells within the aggregates.

Acetylcholine↗
PubMed1979

Morphological differentiation of mechanically dissociated fetal rat brain in aggregating cell cultures.

Rotation-mediated aggregating cell cultures of mechanically dissociated fetal rat brains (15-16 days) were morphologically characterized at 4, 19, 26 and 40 days in vitro. The dissociated cells coalesced into spherical aggregates which increased in diameter from 340 micrometer at 4 days to 430 micrometer at 40 days. Cells within the aggregates developed from an undifferentiated state at 4 days to a population of morphologically mature neurons, astrocytes and oligodendrocytes (26 days in vitro) before degenerating. Synaptic contacts and myelinated axons appeared as the cells differentiated. Neurons tended to occur in clusters that were located in central regions of the aggregates, whereas astrocytes were more concentrated in the periphery. Synapses and myelinated axons were more abundant in central portions of the aggregates. The amount of myelin formed within the aggregates was less than in organotypic cultures or in vivo. These results show that the morphological differentiation of mechanically dissociated aggregates resembles the development of rat CNS in vitro. The ease with which large amounts of aggregates can be prepared provides an in vitro system which can be analyzed biochemically without the use of micro-methods. This advantage is particularly useful for multidisciplinary investigations in developmental neurobiology.

Animals↗
PubMed1979

Series on pharmacology in practice: 1. Drugs that alter mood. I. Tricyclic agents and monoamine oxidase inhibitors.

In the last 20 years, the treatment of mood disorders has advanced immeasurably. We now have relatively safe and effective agents for the treatment of depression and mania. This review discusses two types of agents that elevate mood--tricyclic antidepressants and monoamine oxidase inhibitors--including the indications for their use and their modes of action, pharmacokinetics, side effects, and drug interactions.

Antidepressive Agents, Tricyclic↗
PubMed1979

Mayo Seminars in Psychiatry: dopamine and schizophrenia--a review.

Considerable evidence exists linking dopamine with schizophrenia. Other neurotransmitters including acetylcholine, serotonin and gamma-aminobutyric acid (GABA) are also being implicated. Neurotransmitters act via receptors on brain cells and evidence suggests that antipsychotic drugs exert their therapeutic actions and produce side effects by receptor blockade.

Animals↗
PubMed1979

Tricyclic antidepressants and histamine H1 receptors.

Tricyclic antidepressants and some structurally related compounds were tested for their ability to antagonize histamine H1 and muscarinic acetylcholine receptors of cultured mouse neuroblastoma cells. As a group, tertiary amine tricyclic antidepressants tended to be more potent than secondary amine drugs at both receptors. The most potent antihistamine, doxepin hydrocholoride, was about 4 times more potent than amitriptyline hydrochloride, about 800 times more potent than diphenhydramine hydrochloride, and about 8,000 times more potent than desipramine hydrochloride, the least potent tricyclic antidepressant at both the histamine H1 and the muscarinic acetylcholine receptors. All tricyclic drugs except desipramine hydrochloride were more potent as antihistamines than as anticholinergics. Doxepin hydrochloride and amitriptyline hydrochloride may be the most potent antihistamines known, and the antihistaminic potencies of these and the other tricyclic antidepressant drugs may relate directly to their ability to cause sedation and drowsiness in patients.

Amitriptyline↗
PubMed1979

Series on pharmacology in practice. 1. Drugs that alter mood. II. Lithium.

In the last two decades, there has been rapid progress in the pharmacologic treatment of affective disorders. In Part I of this review, drugs mainly used for depression (tricyclic antidepressants and monoamine oxidase inhibitors) were discussed. Here, lithium carbonate, the most effective drug for manic-depressive illness (bipolar depression) is the focus. Its indications, mode of action, pharmacokinetics, dosage, and side effects are discussed. A section on drug interactions with lithium deals with the combination effect of lithium used with antidepressant and other psychotropic agents.

Abnormalities, Drug-Induced↗