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GABAA receptor positive allosteric modulator
In pharmacology, GABAA receptor positive allosteric modulators, also known as GABAkines or GABAA receptor potentiators, are positive allosteric modulator (PAM) molecules that increase the activity of the GABAA receptor protein in the vertebrate central nervous system.
GABA is a major inhibitory neurotransmitter in the central nervous system. Upon binding, it triggers the GABAA receptor to open its chloride channel to allow chloride ions into the neuron, making the cell hyperpolarized and less likely to fire. GABAA PAMs increase the effect of GABA by making the channel open more frequently or for longer periods. However, they have no effect if GABA or another agonist is not present.
Unlike GABAA receptor agonists, GABAA PAMs do not bind at the same active site as the γ-aminobutyric acid (GABA) neurotransmitter molecule: they affect the receptor by binding at a different site on the protein. This is called allosteric modulation.
In psychopharmacology, GABAA receptor PAMs used as drugs have mainly sedative and anxiolytic effects. Examples of GABAA PAMs include ethanol, benzodiazepines such as diazepam (Valium) and alprazolam (Xanax), Z-drugs such as zolpidem (Ambien) and the barbiturate drugs.
The GABAA receptors have historically been a target of drug treatment research. The earliest compounds were ionic compounds, such as bromide.
In 1903, the first psychoactive derivative of barbituric acid was synthesized and marketed for headaches. Within 30 years, many other barbiturates were developed and found use as sedatives, sleep aids and general anesthetics. Although barbiturates fell out of favor, they continue to serve as a short-acting anesthetic and anti-epileptic drugs.
Benzodiazepines were discovered in 1955 and largely replaced the barbiturates because of their larger therapeutic index. At first benzodiazepines were considered to be safe and efficient minor tranquilizers but then were criticized for their dependence producing effects. Several efficient benzodiazepines offer choices about dosage form, length of action, metabolic interaction and safety.
Benzodiazepines function by binding to the benzodiazepine site on most, but not all, GABAA receptors. GABAA modulation by benzodiazepine site agonists is self-limiting. The channel conductance is not higher in the presence of benzodiazepine and GABA than the conductance with the presence of only high GABA concentrations. Additionally, in the absence of GABA the presence of benzodiazepines alone does not open the chloride channel.
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GABAA receptor positive allosteric modulator
In pharmacology, GABAA receptor positive allosteric modulators, also known as GABAkines or GABAA receptor potentiators, are positive allosteric modulator (PAM) molecules that increase the activity of the GABAA receptor protein in the vertebrate central nervous system.
GABA is a major inhibitory neurotransmitter in the central nervous system. Upon binding, it triggers the GABAA receptor to open its chloride channel to allow chloride ions into the neuron, making the cell hyperpolarized and less likely to fire. GABAA PAMs increase the effect of GABA by making the channel open more frequently or for longer periods. However, they have no effect if GABA or another agonist is not present.
Unlike GABAA receptor agonists, GABAA PAMs do not bind at the same active site as the γ-aminobutyric acid (GABA) neurotransmitter molecule: they affect the receptor by binding at a different site on the protein. This is called allosteric modulation.
In psychopharmacology, GABAA receptor PAMs used as drugs have mainly sedative and anxiolytic effects. Examples of GABAA PAMs include ethanol, benzodiazepines such as diazepam (Valium) and alprazolam (Xanax), Z-drugs such as zolpidem (Ambien) and the barbiturate drugs.
The GABAA receptors have historically been a target of drug treatment research. The earliest compounds were ionic compounds, such as bromide.
In 1903, the first psychoactive derivative of barbituric acid was synthesized and marketed for headaches. Within 30 years, many other barbiturates were developed and found use as sedatives, sleep aids and general anesthetics. Although barbiturates fell out of favor, they continue to serve as a short-acting anesthetic and anti-epileptic drugs.
Benzodiazepines were discovered in 1955 and largely replaced the barbiturates because of their larger therapeutic index. At first benzodiazepines were considered to be safe and efficient minor tranquilizers but then were criticized for their dependence producing effects. Several efficient benzodiazepines offer choices about dosage form, length of action, metabolic interaction and safety.
Benzodiazepines function by binding to the benzodiazepine site on most, but not all, GABAA receptors. GABAA modulation by benzodiazepine site agonists is self-limiting. The channel conductance is not higher in the presence of benzodiazepine and GABA than the conductance with the presence of only high GABA concentrations. Additionally, in the absence of GABA the presence of benzodiazepines alone does not open the chloride channel.