Pre-Botzinger complex

The Pre-Bötzinger Complex (preBötC) is a cluster of interneurons in the ventrolateral medulla essential to the generation of respiratory rhythm in mammals. The exact mechanism of the rhythm generation and transmission to motor nucluei remains controversial and the topic of much present research.

Several synthetic compounds have been shown to act on neurons specfic to the preBötC, most being selective agonists or antagonists to receptor subtypes on neurons in the vicinity. Since many of these neurons express GABA, NMDA-glutamate, 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 stem, called BIMU8, has been discovered. BIMU8, a selective 5HT4 serotonin agonist is thought to stimulate the preBötC, causing an increase in the rate of respiration. 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 CGS21680 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.