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H C Sabelli

Publications and source records attributed to H C Sabelli.

12 recordsLinked to original sources
PubMed1978

Lithium prevention of amphetamine-induced 'manic' excitement and of reserpine-induced 'depression' in mice: possible role of 2-phenylethylamine.

Repeated treatment of mice with lithium chloride (45 mg/kg, i.p., daily for 8 days) reduced the jumping, fighting, stereotypies, and hyperactivity induced by d-amphetamine (5 mg/kg, i.p.). Lithium also reduced the hypoactivity observed 1--3 h after reserpine (0.75 mg/kg, i.p.). In biochemical studies we found that 8-day treatment with lithium markedly reduced (to 45% of control) the recovery from brain of labelled 2-phenylethylamine (PEA) following i.p. injection of labelled L-phenylalanine, while decreasing recovery from brain of labelled PEA following its i.p. injection of 63% of control. In saline-treated mice, d-amphetamine appeared to increase PEA synthesis and to accelerate its disposition, whereas reserpine enhanced PEA synthesis and reduced disposition; all of these effects were antagonized by lithium pretreatments. Since PEA appears to be one of the most powerful behavioral stimulants among endogenous neuroamines, and because its deaminated metabolites are behavioral depressants, such antagonism of brain PEA metabolism may significantly contribute to the prophylactic action of lithium against both manic and depressive behavior.

Animals↗
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↗
PubMed1975

Behavioral and electrophysiological effects of phenylethanolamine and 2-phenylethylamine.

The electrophysiological and behavioral effects of phenylethanolamine (OHPEA) and of its precursor 2-phenylethylamine (PEA) were studied in mice and rabbits. In animals pretreated with MAOI, PEA was found to exert strong amphetamine-like effects, EEG alerting, reduction of visual evoked responses, increased locomotor activity, and blockade of tonic seizures induced by electroshock. OHPEA exerted weaker amphetamine-like effects. Inhibition of dopamine-beta-hydroxylase increased most of the effects of PEA. In non-pretreated animals, OHPEA was found to shorten electroshock latency and to prolong the duration of visual evoked responses. PEA (but not OHPEA) potentiated the excitement induced by delta9-tetrahydrocannabinol in MAOI-pretreated mice. Reserpine pretreatment reduced but did not abolish the CNS effects of OHPEA and PEA. One may speculate that endogenous PEA is more likely to serve as a modulator for ergotropic functions than is endogenous OHPEA.

Animals↗
PubMed1975

Differential membrane effects of general and local anesthetics.

The authors studied the effects of varying Na+ and Ca++ concentrations and of replacing H2O with D2O in Ringer's solution upon the actions of general and local anesthetics on isolated frog sciatic nerves. This experimental model was used to study whether general anesthetics affect excitable membranes in a manner similar to that of typical membrane stabilizers (local anesthetics). Procaine (2.5-7.5 mM), halothane (9, 18, and 36 mM), enflurane (8 mM), and ketamine (0.15 and 0.73 mM) raised threshold and lowered spike amplitude, and their effects were facilitated by reducing Na+ concentration in the Ringer's solution. The local anesthetic effects of procaine (2.5-7.5 mM) and ketamine (0.73 mM) were antagonized by Ca++, while the axonal depressant effect of halothane was facilitated by increasing Ca++ concentration in the Ringer's solution, indicating a different mode of action. General anesthetics also differed from local anesthetics in their interaction with water: replacement by D2O of H2O in the Ringer's solution selectively increased the axonal depressant effects of halothane and enflurane but not those of ketamine or procaine. Since D2O differs from H2O in its greater ice-likeness, these results are consistent with the view that general anesthetics stabilize excitable membranes via stabilization of the water-biopolymer lattice, as predicted by the hydrate-microcrystal theory of anesthesia. In contrast, local anesthetics may stabilize excitable tissues by binding to the same fixed negative charges of the membrane to which Ca++ is normally bound. (Key words: Theories of anesthesia, hydrate-microcrystal; Nerve, mode of action of anesthetics; Anesthetics, volatile, halothane; Anesthetics, volatile, enflurane; Anesthetics, local, procaine; Anesthetics, intravenous, ketamine.)

Anesthesia, General↗
PubMed1975

Differential effects of phenobarbital and pentobarbital on isolated nervous tissue.

Epileptiform after discharges evoked by repetitive electrical stimulation of chronically isolated cortical slabs (cat) were shortened by low doses of phenobarbital but not affected by hypnotic doses of pentobarbital. Both pentobarbital and phenobarbital raised threshold and lowered spike amplitude in isolated sciatic nerves. The action of both drugs was increased by reducing Na in the medium and by decreasing the Ringer's pH. Similar to the action of other general anesthetics, the axonal effect of pentobarbital was enhanced by D2O replacement for H2O in the Ringer's (suggesting that tissue water is involved in pentobarbital action), whereas D2O replacement did not modify the action of phenobarbital or of local anesthetics. These results suggest that the varying in vivo effects of pentobarbital and phenobarbital may be due to a difference in their action upon excitable membranes (rather than to a different regional distribution in brain).

Animals↗