Effect of 1,4-butanediol and other butyric acid congeners on brain catecholamines

Gessa, Gian Luigi; Spano, Pier Franco; Vargiu, L; Crabai, F; Tagliamonte, A.; Mameli, Laura

doi:10.1016/0024-3205(68)90202-6

Cited by 30 publications

(3 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has also been shown that HOBA can produce a sleep-like state simultaneously with a remarkably persistent rightingreflex (Basil et al, 1964), which is strikingly similar to the behavioural effects of HA-966. More recently GABA, HOBA and some other structurally related analogues were shown to increase selectively striatal dopamine levels (Gessa, Spano, Vargiu, Crabai, Tagliamonte & Mameli, 1968). Inhibition of dopamine release from striatal neurones has also been suggested for butyrolactone (Roth & Suhr, 1970).…”

Section: Discussionmentioning

confidence: 99%

1‐Hydroxy‐3‐amino‐pyrrolidone‐2 (HA‐966): a new GABA‐like compound, with potential use in extrapyramidal diseases

Bonta

Vos²,

Grijsen³

et al. 1971

British J Pharmacology

View full text Add to dashboard Cite

Summary1. The drug HA-966 (1-hydroxy-3-amino-pyrrolidone-2), which chemically resembles the cyclic form of GABA, has been studied for neuro-pharmacological properties and for effects on the catecholamine content of the corpus striatum. 2. The acute effects on spontaneous behaviour of rodents included flaccid catalepsy and reversible tranquillization in doses which were 5% or less of the lethal dose. Long lasting depression of the CNS, followed by complete recovery, was produced in the cat and the dog. In the monkey HA-966 caused periodical sleeping episodes. 3. The exploratory behaviour and the amphetamine-induced motor activity in mice were blocked by HA-966. The toxicity of amphetamine in aggregated mice was only moderately reduced, suggesting that HA-966 differs from neuroleptics. 4. Tremors induced by chemical agents (nicotine, zinc and tremorine) were markedly inhibited by HA-966. The muscarinic effects of tremorine were not reduced by HA-966, indicating a selective central antitremor effect. 5. HA-966 elevated the threshold to strychnine convulsions and abolished the ipsilateral flexor reflex, while not having motor endplate blocking properties. It is suggested that HA-966 depresses central internuncial neurones. 6. In rats and rabbits HA-966 produced synchronous EEG and inhibited the sensory arousal in doses not causing sedation. In the monkey the drug caused a periodical dissociation between 'sleep-EEG' and behaviour. 7. In rat brain, HA-966 selectively elevated the dopamine content in the corpus striatum, while no changes in noradrenaline and 5-hydroxytryptamine contents could be demonstrated. The effect was still present when dopa synthesis was inhibited with a-methyl-p-tyrosine. 8. Several effects of intravenously administered HA-966 became manifest after an appreciable delay and in hepatectomized mice the effects were much reduced. It is postulated that HA-966 is converted to a pharmacologically active metabolite.HA -966, drug for extrapyramidal diseases 9. The results are discussed in the light of current views on drug therapy in extrapyramidal conditions and a GABA-related hypothesis as to the mode of action of HA-966 is presented.

show abstract

Section: Discussionmentioning

confidence: 99%

1‐Hydroxy‐3‐amino‐pyrrolidone‐2 (HA‐966): a new GABA‐like compound, with potential use in extrapyramidal diseases

Bonta

Vos²,

Grijsen³

et al. 1971

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Succinic acid at 1.5 f 12 mg/kg elicited significant anxiolytic effect and did not cause the change of motor activity. Gessa et al reported that succinic acid induced a central depressant action at high doses, for example sedation at 4000 mg/kg (Gessa et al, 1968), this dose are 2666 times higher than the minimum dose for significant anxiolytic effect (1.5 mg/kg, IP). Thus it is expected that when the anxiolytic effect is considered as the main effect, the central depressant effect of succinic acid is very weak.…”

Section: Discussionmentioning

confidence: 96%

“…It has been reported that succinic acid had sedative effect (4000 mg/kg) and protective action against high pressure oxygen convulsion (1180 mg/kg) (Sanders et al, 1969;Gessa et al, 1968). Jin et al also reported that succinic acid at dose of 1180 mg/kg produced significant decrease of the locomotor activity and hyperthermia and prolonged the pentobarbital sleeping time significantly in mice.…”

Section: Introductionmentioning

confidence: 97%