Actions of bupivacaine, a widely used local anesthetic, on NMDA receptor responses.

NMDA receptors mediate excitatory neurotransmission in brain and spinal cord and play a pivotal role in the neurological disease state of chronic pain, which is caused by central sensitization. Bupivacaine is the indicated local anesthetic in caudal, epidural, and spinal anesthesia and is widely used clinically to manage acute and chronic pain. In addition to blocking Na(+) channels, bupivacaine affects the activity of many other channels, including NMDA receptors.

One-channel cell-attached patch-clamp recording.

Ion channel proteins are universal devices for fast communication across biological membranes. The temporal signature of the ionic flux they generate depends on properties intrinsic to each channel protein as well as the mechanism by which it is generated and controlled and represents an important area of current research. Information about the operational dynamics of ion channel proteins can be obtained by observing long stretches of current produced by a single molecule.

Role of cross-cleft contacts in NMDA receptor gating.

In response to brief glutamate exposure, NMDA receptors produce excitatory currents that have sub-maximal amplitudes and characteristically slow kinetics. The activation sequence starts when glutamate binds to residues located on the upper lobe of extracellularly located ligand-binding domains (LBDs) and then contacts lower lobe residues to bridge the cleft between the two hinged lobes. This event stabilizes a narrow-cleft LBD conformation and may facilitate subsequent inter-lobe contacts that further stabilize the closed cleft.

An interactive lesson in acid/base and pro-drug chemistry using sodium gamma-hydroxybutyrate and commercial test coasters.

Objective: To develop a classroom activity that applied pertinent pharmaceutical concepts to examine the use and limitations of a commercially available test drink coaster in detecting the presence of a date-rape drug, sodium gamma-hydroxybutyrate (NaGHB), in beverages.

Design: An activity exercise involving a combination of self-study, hands on participation, and classroom discussion was developed. Topics incorporated into the activity were drug-assisted rape, the concepts of false positives and negatives, and prodrug and pH chemistry.