Chapter title |
Chronic administration of the antidepressant phenelzine and its N-acetyl analogue: effects on GABAergic function.
|
---|---|
Chapter number | 15 |
Book title |
Amine Oxidases: Function and Dysfunction
|
Published in |
Journal of neural transmission Supplementum, January 1994
|
DOI | 10.1007/978-3-7091-9324-2_15 |
Pubmed ID | |
Book ISBNs |
978-3-21-182521-1, 978-3-70-919324-2
|
Authors |
McKenna, K F, McManus, D J, Baker, G B, Coutts, R T, McKenna, K. F., McManus, D. J., Baker, G. B., Coutts, R. T., K. F. McKenna, D. J. McManus, G. B. Baker, R. T. Coutts |
Abstract |
The MAO inhibitor phenelzine (2-phenylethylhydrazine; PLZ) is used widely in psychiatry for the treatment of depression and panic disorder. Its N-acetyl metabolite, N2-acetylphenelzine (N2AcPLZ) is a reasonably potent nonselective inhibitor of monoamine oxidase (MAO) that causes elevation in brain levels of the biogenic amines. In the studies reported here, PLZ (0.05 mmol/kg/day), N2AcPLZ (0.10 mmol/kg/day) or vehicle were administered to male rats for 28 days s.c. with Alzet minipumps, and their effects on GABAergic function were examined. Whole brain concentrations of gamma-aminobutyric acid (GABA) were significantly elevated in the PLZ but not in the N2AcPLZ-treated group. PLZ was found to inhibit the anabolic enzyme glutamic acid decarboxylase (GAD) and, to a greater extent, the catabolic enzyme GABA transaminase (GABA-T). The results of these investigations suggest that the free hydrazine moiety in PLZ is crucial to producing the elevated levels of GABA, probably through inhibition of GABA-T. Despite the considerable increase in whole brain GABA levels in the PLZ-treated rats, there were no significant differences in GABAA or benzodiazepine receptor binding parameters (KD or Bmax) between the groups as measured using 3H-muscimol and 3H-flunitrazepam in radioligand binding assays. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 12 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 2 | 17% |
Student > Bachelor | 2 | 17% |
Lecturer | 1 | 8% |
Professor | 1 | 8% |
Professor > Associate Professor | 1 | 8% |
Other | 0 | 0% |
Unknown | 5 | 42% |
Readers by discipline | Count | As % |
---|---|---|
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 8% |
Biochemistry, Genetics and Molecular Biology | 1 | 8% |
Agricultural and Biological Sciences | 1 | 8% |
Psychology | 1 | 8% |
Medicine and Dentistry | 1 | 8% |
Other | 1 | 8% |
Unknown | 6 | 50% |