Pre-Botzinger complex
Encyclopedia
The Pre-Bötzinger Complex (preBötC) is a cluster of interneuron
s in the ventrolateral medulla
of the brainstem, which is essential to the generation of respiratory rhythm
in mammals. The exact mechanism of the rhythm generation and transmission to motor nuclei remains controversial and the topic of much present research.
Several synthetic compounds have been shown to act on neurons specific to the preBötC, most being selective agonists or antagonists to receptor subtypes on neurons in the vicinity. Since many of these neurons express GABA
, glutamate, serotonin
and adenosine receptors, chemicals custom tailored to bind at these sites are most effective at altering respiratory rhythm.
One such novel compound that acts on this area of the brain, called BIMU8
, has been discovered. BIMU8, along with other selective serotonin
5HT4 receptor
agonist
s such as zacopride
, are thought to stimulate the preBötC, causing an increase in the rate of respiration which can block the respiratory depression produced by high doses of opioid
drugs. Several ampakine
drugs, such as CX-546, CX-717 and CX-1739, also stimulate this area, and some of these are being developed for use alongside opioids in human medicine.
Adenosine modulates the preBötC output via activation of the A1 and A2A receptor subtypes. An adenosine A1 receptor agonist called N6-Cyclopentyladenosine
(NCPA) has been shown to depress preBötC rhythmogenesis independent of the neurotransmitters GABA and glycine in "in vitro" preparations from 0-7 day old mice. Another synthetic drug specific to the adenosine A2A receptor subtype is CGS-21680 that has been shown to cause apneas in 14-21 day old rat pups in vivo. For this reason, it has been used as a model to study pathological conditions such as apnea of prematurity and SIDS in neonatal infants.
Interneuron
An interneuron is a multipolar neuron which connects afferent neurons and efferent neurons in neural pathways...
s in the ventrolateral medulla
Medulla oblongata
The medulla oblongata is the lower half of the brainstem. In discussions of neurology and similar contexts where no ambiguity will result, it is often referred to as simply the medulla...
of the brainstem, which is essential to the generation of respiratory rhythm
Control of respiration
Control of ventilation refers to the physiological mechanisms involved in the control of physiologic ventilation. Gas exchange primarily controls the rate of respiration.The most important function of breathing is gas exchange...
in mammals. The exact mechanism of the rhythm generation and transmission to motor nuclei remains controversial and the topic of much present research.
Several synthetic compounds have been shown to act on neurons specific to the preBötC, most being selective agonists or antagonists to receptor subtypes on neurons in the vicinity. Since many of these neurons express GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
, glutamate, serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
and adenosine receptors, chemicals custom tailored to bind at these sites are most effective at altering respiratory rhythm.
One such novel compound that acts on this area of the brain, called BIMU8
BIMU8
BIMU-8 is a drug which acts as a 5-HT4 receptor selective agonist. BIMU-8 was one of the first compounds of this class. The main action of BIMU-8 is to increase the rate of respiration by activating an area of the brain stem known as the pre-Botzinger complex....
, has been discovered. BIMU8, along with other selective serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
5HT4 receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
s such as zacopride
Zacopride
Zacopride is a potent antagonist at the 5HT3 receptor and an agonist at the 5HT4 receptor. It has anxiolytic and nootropic effects in animal models, with the enantiomer being the more active form...
, are thought to stimulate the preBötC, causing an increase in the rate of respiration which can block the respiratory depression produced by high doses of opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
drugs. Several ampakine
Ampakine
Ampakines are a class of compounds known to enhance attention span and alertness, and facilitate learning and memory. The ampakines take their name from the glutamatergic AMPA receptor with which they strongly interact...
drugs, such as CX-546, CX-717 and CX-1739, also stimulate this area, and some of these are being developed for use alongside opioids in human medicine.
Adenosine modulates the preBötC output via activation of the A1 and A2A receptor subtypes. An adenosine A1 receptor agonist called N6-Cyclopentyladenosine
N6-Cyclopentyladenosine
N6-Cyclopentyladenosine is a drug which acts as a selective adenosine A1 receptor agonist. It has mainly cardiovascular effects with only subtle alterations of behaviour. CPA is widely used in scientific research into the adenosine receptors and has been used to derive a large family of derivatives....
(NCPA) has been shown to depress preBötC rhythmogenesis independent of the neurotransmitters GABA and glycine in "in vitro" preparations from 0-7 day old mice. Another synthetic drug specific to the adenosine A2A receptor subtype is CGS-21680 that has been shown to cause apneas in 14-21 day old rat pups in vivo. For this reason, it has been used as a model to study pathological conditions such as apnea of prematurity and SIDS in neonatal infants.