Gamma-aminobutyric Acid Mimetics Research Articles

Phenibutan-an Illegal Food Supplement With Psychotropic Effects and Health Risks.

Phenibut (β-phenyl-γ-aminobutyric acid) is an analog of the neurotransmitter gamma-aminobutyric acid (GABA). Like abapentin and pregabalin, it inhibits α2-δ-subunits of voltagedependent presynaptic calcium channels. The potential harm resulting from the use of these gabapentinoids is currently a matter of debate. This review is based on pertinent publications retrieved by a selective literature search and on cases reported to the Giftinformationszentrum-Nord (GIZ-Nord), a poison information center at the University of Göttingen, Germany. Phenibut is a prescription drug in Russia but its production, possession, use, trafficking, or administration is illegal in Germany. The phenibut toxicity syndrome resembles that of gabapentinoids and GABA mimetics: benzodiazepine-like with - drawal symptoms including epileptic seizures, delirium and paradoxical activation have been described, as have cases of abuse and dependence. A few cases of use in the setting of multidrug abuse, and of phenibut-related death, have been described to date in the USA. The GIZ-Nord received 17 inquiries about phenibut, 55 about gabapentin, and 126 about pregabalin over the period 2008-2022. Over the same period, the GIZ-Nord was informed of 1207 cases involving Z substances and 4324 involving benzodiazepines. In the majority of the registered intoxications, including those with phenibut, the symptoms were mild. Overdoses of phenibut (2-100 g) were reported in 15 of the 17 cases; 8 of the persons who had taken an overdose were somnolent. In such cases, observation in intensive care was recommended. Respiratory depression or coma was not encountered in any case, not even in the patient who had taken 100 g of phenibut. Phenibut causes symptoms resembling those of gabapentinoid and benzodiazepine use. There have been reports of phenibut use in combination with other psychotropic drugs; in particular, its use together with opiates could increase the risk of coma and respiratory depression. No deaths due to phenibut intoxication have been published in Germany or elsewhere in Western Europe, although such cases may have been overlooked, as this drug is still largely unknown to Western medicine.

Management of cancer pain: 1. Wider implications of orthodox analgesics

In this review, the first of two parts, we first provide an overview of the orthodox analgesics used commonly against cancer pain. Then, we examine in more detail the emerging evidence for the potential impact of analgesic use on cancer risk and disease progression. Increasing findings suggest that long-term use of nonsteroidal anti-inflammatory drugs, particularly aspirin, may reduce cancer occurrence. However, acetaminophen may raise the risk of some hematological malignancies. Drugs acting upon receptors of gamma-aminobutyric acid (GABA) and GABA “mimetics” (eg, gabapentin) appear generally safe for cancer patients, but there is some evidence of potential carcinogenicity. Some barbiturates appear to slightly raise cancer risks and can affect cancer cell behavior in vitro. For cannabis, studies suggest an increased risk of squamous cell carcinoma of the tongue, larynx, and possibly lung. Morphine may stimulate human microvascular endothelial cell proliferation and angiogenesis; it is not clear whether this might cause harm or produce benefit. The opioid, fentanyl, may promote growth in some tumor cell lines. Opium itself is an emerging risk factor for gastric adenocarcinoma and possibly cancers of the esophagus, bladder, larynx, and lung. It is concluded that analgesics currently prescribed for cancer pain can significantly affect the cancer process itself. More futuristically, several ion channels are being targeted with novel analgesics, but many of these are also involved in primary and/or secondary tumorigenesis. Further studies are needed to elucidate possible cellular and molecular effects of orthodox analgesics and their possible long-term impact, both positive and negative, and thus enable the best possible clinical gain for cancer patients.

Effect of gamma-butyrolactone on baclofen inhibition of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effect of gamma-butyrolactone (GBL) on inhibition by baclofen of gastric carcinogenesis was investigated in Wistar rats. In week 52, baclofen significantly decreased the incidence of gastric cancers. Concomitant treatment with GBL significantly increased gastric acid secretion but had no influence on the inhibition by baclofen of gastric carcinogenesis. This finding suggest that GBL significantly increased the sensitivity of gamma-aminobutyric acid (GABA) receptor to GABA mimetics in gastric acid secretion but not in the inhibitory effect of gastric carcinogenesis.

Prolonged treatment with gamma-aminobutyric acid (GABA)-mimetic substances in prepubertal male rats.

The effect of chronic treatment with a gamma-aminobutyric acid (GABA)-mimetic compound, progabide, and an inhibitor of GABA-transaminase, gamma-acetylenic GABA (GAG), was tested in prepubertal male rats. The effect of gamma-butyrolactone (GBL), given orally, was also tested. The rats treated with progabide did not show any difference in body, testicular, or seminal vesicle weights or serum prolactin levels, as compared with control rats. Treatment with GAG, at both dose levels used, did not significantly affect body weight. Testicular weight was significantly lower in the group of rats treated with the low dosage of GAG (5 mg/kg), and serum prolactin was significantly lower in the rats treated with the high dosage of GAG (20 mg/kg) as compared with control rats. In the first experiment performed with GBL, the rats given this compound had significantly lower body and testicular weights as compared with control rats. In the second experiment, GBL-treated rats had body weights similar to those of control rats, but testicular weights were significantly decreased. Prolonged treatment with GABA mimetics may affect the hypothalamic-pituitary-testicular axis.