Gamma-aminobutyric acid: Difference between revisions
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'''Gamma aminobutyric acid''' (GABA) or <math>\gamma</math>-aminobutyrate, is | '''Gamma aminobutyric acid''' (GABA) or <math>\gamma</math>-aminobutyrate, is the major inhibitory [[neurotransmitter]] in the [[central nervous system]].<ref name="isbn0-07-145153-6">{{cite book |author=Katzung, Bertram G. |title=Basic and clinical pharmacology |publisher=McGraw-Hill Medical Publishing Division |location=New York |year=2006 |pages= |isbn=0-07-145153-6 |oclc= |doi=}}</ref> GABA is produced from the [[amino acid]] glutamate through the action of the enzyme [[glutamate decarboxylase]], and is inactivated by degradation to [[succinate]] in a two step mechanism involving the enzymes [[GABA-glutamate transaminase]] and [[succinate semialdehyde dehydrogenase]]. | ||
==Receptors== | |||
GABA<sub>A</sub> is the most prominent.<ref name="G&G_Chapt11">Bloom Floyd E, "Chapter 12. Neurotransmission and the Central Nervous System" (Chapter). Brunton LL, Lazo JS, Parker KL: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11e: http://www.accessmedicine.com/content.aspx?aID=937279.</ref> Many medications, many neuroactive drugs (see Chapters 16 and 22), "[[benzodiazepine]]s, [[barbiturate]]s, [[ethanol]], anesthetic steroids, and [[volatile anesthetic]]s", act on the GABA<sub>A</sub> receptor.<ref name="G&G_Chapt11"/> | |||
GABA<sub>B</sub> "function as autoreceptors, inhibiting GABA release".<ref name="G&G_Chapt11"/> | |||
GABA<sub>C</sub> is less widely distributed and is in the [[retina]], [[spinal cord]], superior colliculus, and [[pituitary gland]]. GABA<sub>C</sub> receptors are not affected by the agonist [[baclofen]] or the modulators [[benzodiazepine]]s and [[barbiturate]]s.<ref name="G&G_Chapt11"/> | |||
==Role in clinical pharmacology== | |||
{{main|GABA modulator}} | |||
GABA modulators have various roles. | |||
===Gamma-aminobutyric acid (GABA) (physiologic) agonists=== | |||
{| class="wikitable" align="right" | |||
|+ Selected GABA agonists<ref>Charney Dennis S, Mihic S. J, Harris R. A, "[http://www.accessmedicine.com/content.aspx?aID=938413 Chapter 16. Hypnotics and Sedatives]" (Chapter). Brunton LL, Lazo JS, Parker KL: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11e:.</ref> | |||
! Half life<br/>(may not relate to duration of effect)!! Benzodiazepines!!Other | |||
|- | |||
| short (< 6 hrs)|| [[midazolam]] (1-4 hrs)<br/>[[triazolam]] (1.5-5.5 hrs)<br/>oxazepam (2.8-5.7 hrs)||zolpidem (2 hrs)<br/>zopiclone (5-6 hrs) | |||
|- | |||
| intermediate (6 - 24 hrs)|| [[alprazolam]]<br/>estazolam<br/>[[lorazepam]]<br/>[[temazepam]] | |||
|- | |||
| long (> 24 hrs)|| [[chlordiazepoxide]]<br/>[[flurazepam]]<br/>[[diazepam]]<br/>quazepam. | |||
|- | |||
|} | |||
Drugs that increase the effect or secretion of GABA are called GABAergic, such as [[baclofen]]. | |||
Many sedatives work by increasing receptiveness of GABA<sub>A</sub> receptors. | |||
====Barbituates==== | |||
[[Barbituates|Barbituates]] are GABAergic by increasing receptiveness of the GABA<sub>A</sub> receptors. Barbituates do this by increasing the duration of openings of channels in the cell membrane.<ref name="isbn0-07-145153-6"/> | |||
* Phenobarbital | |||
====Gabapentin & Pregabalin==== | |||
[[Gabapentin]] and [[pregabalin]] are both analogs that are agonists of GABA. | |||
====Nonselective BZ<sub>1</sub> and BZ<sub>2</sub> agonists==== | |||
[[Benzodiazepine]]s are also nonselective GABAergic by increasing receptiveness of the GABA<sub>A</sub> receptors. However, benzodiazepines do this by increasing the frequency of openings of channels in the cell membrane.<ref name="isbn0-07-145153-6"/> | |||
[[Benzodiazepine]] receptors are BZ<sub>1</sub> and BZ<sub>2</sub>. | |||
====BZ<sub>1</sub> selective agonists==== | |||
Cyclopyrrolones / Piperazines | |||
* [[Zopiclone]] | |||
* [[Eszopiclone]] | |||
Imidazopyridines | |||
* [[Zolpidem]] (Ambien) | |||
Pyrazolopyrimidines | |||
* [[Zaleplon]] (Sonata; Starnoc). May have similar abuse potential to [[Benzodiazepine]]s.<ref name="pmid10445371">{{cite journal| author=Rush CR, Frey JM, Griffiths RR| title=Zaleplon and triazolam in humans: acute behavioral effects and abuse potential. | journal=Psychopharmacology (Berl) | year= 1999 | volume= 145 | issue= 1 | pages= 39-51 | pmid=10445371 | |||
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10445371 }}></ref> | |||
==References== | |||
<references/> | |||
Latest revision as of 09:47, 30 January 2014
Gamma aminobutyric acid (GABA) or -aminobutyrate, is the major inhibitory neurotransmitter in the central nervous system.[1] GABA is produced from the amino acid glutamate through the action of the enzyme glutamate decarboxylase, and is inactivated by degradation to succinate in a two step mechanism involving the enzymes GABA-glutamate transaminase and succinate semialdehyde dehydrogenase.
Receptors
GABAA is the most prominent.[2] Many medications, many neuroactive drugs (see Chapters 16 and 22), "benzodiazepines, barbiturates, ethanol, anesthetic steroids, and volatile anesthetics", act on the GABAA receptor.[2]
GABAB "function as autoreceptors, inhibiting GABA release".[2]
GABAC is less widely distributed and is in the retina, spinal cord, superior colliculus, and pituitary gland. GABAC receptors are not affected by the agonist baclofen or the modulators benzodiazepines and barbiturates.[2]
Role in clinical pharmacology
GABA modulators have various roles.
Gamma-aminobutyric acid (GABA) (physiologic) agonists
| Half life (may not relate to duration of effect) |
Benzodiazepines | Other |
|---|---|---|
| short (< 6 hrs) | midazolam (1-4 hrs) triazolam (1.5-5.5 hrs) oxazepam (2.8-5.7 hrs) |
zolpidem (2 hrs) zopiclone (5-6 hrs) |
| intermediate (6 - 24 hrs) | alprazolam estazolam lorazepam temazepam | |
| long (> 24 hrs) | chlordiazepoxide flurazepam diazepam quazepam. |
Drugs that increase the effect or secretion of GABA are called GABAergic, such as baclofen.
Many sedatives work by increasing receptiveness of GABAA receptors.
Barbituates
Barbituates are GABAergic by increasing receptiveness of the GABAA receptors. Barbituates do this by increasing the duration of openings of channels in the cell membrane.[1]
- Phenobarbital
Gabapentin & Pregabalin
Gabapentin and pregabalin are both analogs that are agonists of GABA.
Nonselective BZ1 and BZ2 agonists
Benzodiazepines are also nonselective GABAergic by increasing receptiveness of the GABAA receptors. However, benzodiazepines do this by increasing the frequency of openings of channels in the cell membrane.[1]
Benzodiazepine receptors are BZ1 and BZ2.
BZ1 selective agonists
Cyclopyrrolones / Piperazines
Imidazopyridines
- Zolpidem (Ambien)
Pyrazolopyrimidines
- Zaleplon (Sonata; Starnoc). May have similar abuse potential to Benzodiazepines.[4]
References
- ↑ 1.0 1.1 1.2 Katzung, Bertram G. (2006). Basic and clinical pharmacology. New York: McGraw-Hill Medical Publishing Division. ISBN 0-07-145153-6.
- ↑ 2.0 2.1 2.2 2.3 Bloom Floyd E, "Chapter 12. Neurotransmission and the Central Nervous System" (Chapter). Brunton LL, Lazo JS, Parker KL: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11e: http://www.accessmedicine.com/content.aspx?aID=937279.
- ↑ Charney Dennis S, Mihic S. J, Harris R. A, "Chapter 16. Hypnotics and Sedatives" (Chapter). Brunton LL, Lazo JS, Parker KL: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11e:.
- ↑ Rush CR, Frey JM, Griffiths RR (1999). "Zaleplon and triazolam in humans: acute behavioral effects and abuse potential.". Psychopharmacology (Berl) 145 (1): 39-51. PMID 10445371. >