Psychopharmacology communications最新文献

1. The effects of lithium on electrolyte metabolism can be demonstrated in man in acute as well as in long-term lithium treatment. 2. It seems feasible to integrate these lithium effects with effects on biogenic amines to form an integral hypothesis for lithium action in manic-malancholic man. 3. The results are consistent with one of the following two hypotheses: a) that lithium acts by membrane stabilization and/or b) that lithium acts by interplay with magnesium or one or more enzymes. 4. The above findings and hypotheses direct attention to membrane dyfunction as the basic defect in manic-melancholic states. This may find support in preliminary findings of special HL-A profiles in unipolar and bioplar manic-melancholic patentis. 5. A four-type pump-defect model may theoretically account for the various clinical types of affective disorders.

The effect of the d- and l-isomers of amphetamine on the activity of dopaminergic neurons in the substantia nigra zona compacta and noradrenergic neurons in the locus coeruleus was studied in anesthetized and gallamine paralyzed rats using single unit recording techniques. d- and l-Amphetamine administered intravenously were equally effective in depressing the activity of locus coeruleus cells. However, although d-amphetamine was a potent inhibitor of substantia nigra dopamine containing cells, l-amphetamine was ineffective in causing more than a 45% inhibition of over half of the DA cells studied, even when given in nearly lethal doses. In the remaining dopamine neurons l-amphetamine was only 0.2 to 0.05 times as potent as d-amphetamine in producing both 50 and 100% inhibition of firing rate. These findings, when combined with recent biochemical studies by other authors, suggest that l-amphetamine, at low doses, has a preferential effect on noradrenergic as compared to dopaminergic neurons. The consequences of these findings for the interpretation of studies in which d- and l-amphetamine have been used as pharmacological tools to determine the catecholamine system responsible for a particular behavior in man and animals is discussed.

A single injection of fenfluramine (100 mumol/kg) produced evidence of neurotoxicity in cresyl violet or silver stained sections of rat brain which was restricted to the serotonergic (B-9) cell group located in the ventromedial midbrain tegmentum. Reacting cells throughout this region exhibited an irregular shape and an intense staining of the cytoplasm, while in the caudal 1/4 of this region the reacting cells also exhibited a perineuronal space. These effects were greatly reduced in the rostral 3/4 of B-9 at 14 and 30 days after fenfluramine. In the caudal 1/4 of B-9 the neurotoxic actions remained prominent and included signs of cellular dissolution. These signs of an irreversible degenerative effect of fenfluramine on cells in the caudal 1/4 of the B-9 region were identical to those seen after p-CA, while the effects in the rostral 3/4 of B-9 were not as prominent. The differential neurotoxic effects of fenfluramine and p-CA on cells in the rostral 3/4 of B-9 were associated with a differential effect on serotonin content of hippocampus and amygdala.

Hydroxyzine hydrochloride may produce abnormal ventricular repolarization when given in substratial doses or to susceptible individuals. Phenothiazines, such as thioridazine, tricyclic antidepressants, or antiparkinson drugs, any of which may be given concurrently to psychiatric patients, may augment this effect as well as atropine, quinidine or procainamide. Such EKG abnormalities may increase the likelihood of dysrhythmias and sudden death.

SU-23397 is a unique new hybrid molecule, the animal profile being characteristic of neuroleptic activity. Although the trial was uncontrolled, there appears to be no doubt that SU-23397 exerts antipsychotic activity between 20 mg and 250 mg daily in severely ill schizophrenic patients. Seven of the ten subjects required at least transient antiparkinson medication. Two patients demonstrated premature ventricular contractions. One patient had infrequent PVCs at baseline which increased in frequency with rising dosage. The other patient developed frequent premature ventricular contractions only after active and medication was initiated and was subsequently withdrawn from the study.

Elevation of the media potassium concentration results in an immediate, but transient increase in the rate of respiration in cerebral cortex slices of the rat. As the respiratory burst decrease in intensity, a transient oxidation of the tissue respiratory intermediates is followed by a net reduction. The burst of respiration is accompanied by a large decrease in tissue ATP and phosphocreatine concentrations. ATP and phosphocreatine concentrations are essentially fully recovered within 5-6 min. The apparent increase in ATP hydrolysis during the peak of the respiratory response was not, however, accompanied by increases in the tissue content of ADP and 5'-AMP. Increased deamination of the adenine nucleotides is discussed as a possible mechanism in the large contraction of the total adenine pool observed during the course of the metabolic response to elevated potassium concentrations.

During a four month period, 20 rats treated with subcutaneous injections of chlorpromazine (CPZ), at any dose tested, gained less weight than saline treated controls. However, increased feeding did occur on the first day of CPZ treatment if the animal was drug free for at least two days prior to treatment. The "first day" hyperphagia was a time limited response that did not occur until 8 hours after CPZ injection and lasted only one day. During the period of hyperphagia, treated animals showed increased motivation to obtain food. Although sedation is a marked effect of CPZ and may be the reason for the delayed onset of hyperphagia, sedation with a different drug does not cause hyperphagia. It is suggested that accumulation of a metabolite of CPZ may interfere with the feeding response and cause the hyperphagia to disappear after the first day of treatment.

Phencyclidine produces a dose-dependent ipsilateral rotation in rats with unilateral substantia nigra lesions. This ipsilateral turning is decreased 41% by pretreatment with AMPT and 81% by prior administration of haloperidol. Ipsilateral turning elicited by phencyclidine can also be altered by treatment with cholinergic agents. These findings suggest that phencyclidine may be acting by increasing the availability of dopamine on the intact side of a unilaterally-lesioned substantia nigra rat and that the response can be modulated by alterations in the cholinergic system.

In previous studies we have shown that perphenazine inhibits the metabolism of nortriptyline and imipramine. In this study the metabolism of 14C-imipramine and 14C-desipramine was studied before and during treatment with perphenazine. Studies on the imipramine and desipramine metabolites in urine showed that the major effect of perphenazine is an inhibition of the 2-hydroxylation of imipramine and desipramine. This causes a decreased formation and excretion of non-conjugated and glucuronide bound hydroxy metabolites and accumulation of imipramine and desipramine. There was some relationship between the dose of perphenazine and the decrease in total urinary excretion but the individual variations in response were pronounced (2-3-fold).

A method for the assay of 7-hydroxychlorpromazine in biological fluids is described. The stages of the method are extraction into ether, back extraction into acid, alkalinisation and further extraction into ether, evaporation of the extract to dryness, and gas-chromatography of the extracted material as a silylated derivative using conditions previously described for chlorpromazine. The method is applicable to certain other hydroxylated chlorpromazines, but it is not superior to existing methods for the assay of nonhydroxylated analogues. Only small quantities of 7-hydroxychlorpromazine were detected in the plasma of schizophrenics showing a satisfactory clinical response, even when the compound was present in urine, providing strong evidence that the presence of 7-hydroxychlorpromazine in blood is not a pre-requisite of successful therapy.