Effect of disulfiram on turnover of 5-hydroxytryptamine in rat brain.

Effect of disulfiram on 5-hydroxytryptamine (5-HT) turnover was studied. Treatment with disulfiram caused increases in 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in rat brain. Under the same condition, activity of brain mitochondrial aldehyde dehydrogenase was reduced, however, supernatant aldehyde dehydrogenase and monoamine oxidase activities remained unchanged. Disulfiram had no effect on synthesis rate of 5-HT, but decreased metabolism of 5-HT. Moreover, disulfiram impaired transport of 5-HIAA from brain tissue.     

Two new coumarins in Boenninghausenia albiflora

Two new isomeric coumarins were isolated from leaves of Boenninghausenia albiflora Reichb. Their structures were elucidated as (E)-7-hydroxy-6-(3-hydroxy-3-methyl-1-butenyl)-2(H)-1-benzpyran-2-one and (Z)-7-hydorxy-6-(3-hydroxy-3-methyl-1-butenyl)-2(H)-1-benzopyran-2-one.     

Modification of the effects of naloxone in morphine-dependent mice

Mice were rendered dependent on morphine by mixing morphine with their food (2 mg/g) for three days. Increasing doses of naloxone precipitated dose-dependent withdrawal reactions such as weight loss and jumping. These withdrawal reactions were antagonized by morphine pretreatment. Effects of morphine, such as increased locomotor activity, inhibition of intestinal transport, and analgesia were antagonized by naloxone in both non-dependent and dependent subjects. The antagonist actions of naloxone were increased in dependent subjects; lower doses of naloxone were sufficient to antagonize effects of morphine. The present results confirm earlier studies indicating that precipitation of withdrawal can be antagonized by morphine pretreatment suggesting that withdrawal reactions are due to actions of naloxone at the same receptor at which opioid agonists act. The increased antagonist potency of naloxone in dependent subjects extends earlier results obtained with analgesic effects to several other agonist effects of morphine and is consistent with the interpretation that exposure to an opioid agonist induces a change in the conformation of opioid receptors.     

Amine-catalyzed Racemization of the Imidazoline Derivatives

Protoplast fusion was carried out between a saké brewer’s yeast strain, Saccharomyces cerevisiae Kyokai 7, and a lactose utilizing yeast strain, Kluyveromyces lactis T396. A stable hybrid, PN 13, which was selected from the many resultant fusants, showed physiologically complemented traits with respect to sugar utilization, vitamin requirements and so on. Biochemical investigations also revealed that fusant PN 13 was an intermediate hybrid between the parental strains. In glucose and lactose media, moreover, the fusant grew and produced ethanol at higher rates than K. lactis T396.     

Effects of central monoamine compounds on tranylcypromine-induced barbital-withdrawal convulsions

Challenge with tranylcypromine (Tcp) during barbital (B) withdrawal induces doserelated clonic-tonic convulsion (C-TC), which is also related to the severity of withdrawal signs and their changes with the passage of time. The effects of neuropharmacological agents on the Tcp-induced convulsions were observed. dl-Propranolol, phentolamine, phenoxybenzamine and methysergide had been administered intraperitoneally 20≈30 minutes before Tcp challenge. B-withdrawn rats had been pretreated with α-methyl-p-tyrosine, 5-hydroxytryptophan, p-chlorophenylalanine or reserpine, or with the combination of iproniazid and reserpine (5 hrs after iproniazid administration) before Tcp challenge. α-MT and dl-propranolol inhibited B withdrawal convulsion markedly, though high doses of dl-propranolol rather tended to show a less inhibitory effect on the convulsion. α-Adrenoceptor blockers scarely inhibited the convulsion. Methysergide or 5-HTP failed to inhibit, but PCPA intensified the convulsion. Reserpine, when administered alone, aggravated the convulsion, but when administered after iproniazid, inhibited it significantly. These findings suggested that the balance between the activities of noradrenergic and serotonergic neurons might be of importance in the manifestation of B withdrawal convulsions, the former probably being excitatory and the latter, inhibitory.     

Susceptibility of brain aldehyde metabolizing enzymes to pargyline, disulfiram and diethylmaleate in vivo in rats.

$\text{In vivo}$ susceptibility of mitochondrial (m)- and soluble (s)-aldehyde dehydrogenase (AlDH) and aldehyde reductase (AIR) to three compounds, i.e., pargyline, diethylmaleate and disulfiram in rat brain was studied. In all experiments using the compounds tested, m-AlDH was more significantly inhibited when the low concentration of the substrate (50 μM) was used, as compared with the inhibition of the enzyme in use of high substrate concentration (3.3 mM). Under same condition, little or no inhibition of s-AlDH and AIR was observed. These findings strongly suggest that there are at least two forms of AlDH with different Kms and they have different susceptibility to AlDH inhibitors.     

Effect of opioid agonist-antagonist interaction on morphine dependence in rats

Morphine dependence was induced by treatment with morphine-admixed food (0.25mg/g of food) for 7 days. Withdrawal was precipitated by injecting naloxone (0.5mg/kg, s.c.). Rats treated with morphine exhibited body weight loss upon the naloxone injection. When morphine-dependent rats were injected subcutaneously with morphine, codeine, meperidine and pentazocine 30 min before the naloxone injection, these drugs significantly suppressed the naloxone-precipitated loss of body weight in a dose-dependent manner. However, body weight loss induced through coadministration of naloxone and Mr-2266 BS were not suppressed by morphine pretreatment. These results suggest that opioids protect against naloxone-precipitated loss of body weight, and that mu and kappa opiate receptors play an important role in the protection against naloxone-precipitated withdrawal.     

Effect of tryptophol on pentylenetetrazol and picrotoxin induced convulsion in mice.

The effect of treatment of mice with tryptophol (TOL), a neutral metabolite of tryptophan, on drug-induced convulsion was studied. TOL effectively suppressed both pentylenetetrazol and picrotoxin induced convulsion. Diphenylhydantoin (DPH), a potent inhibitor of brain aldehyde reductase, significantly reduced the anticonvulsant effect of TOL, however, TOL level in brain of DPH-treated mice was rather higher than that of control one. These results strongly suggest that the manifestation of the anticonvulsant effect of TOL requires the conversion of TOL to its active metabolite, indoleacetaldehyde.