The ABCs of psychopharmacology.

Overheard at the water cooler at a psychopharm clinic: "We had better hurry up and use this drug while it still works." In the movie, Hoosiers, Gene Hackman plays a coach of a small-town, Indiana high school basketball team in the 1950s. In one of many compelling scenes, the coach picks up a basketball draws a circle the size of a 50-cent piece, then, pointing to the entire ball states, "This is what there is to know about basketball." Pointing to the half-dollar size circle he declares, "This is what I know about basketball." The movie analogy works for us, the authors. The analogy recognizes the vast amounts of information available, suggests our limitations, and encourages us to expand our circle. It reminds us to address issues with a certain amount of humility because we are always scratching the surface of what could be said. Coach Hackman wraps up his visual lesson by punching a single dot on the ball with his pen. "This is what you know about basketball." His final point reminds us that to some others (e.g., patients, students), we represent a point of entry into this large body of information. We need to keep on learning. The following represents what the authors believe to be a straightforward and valid approach to conceptualizing psychopharmacology. Heuristic uses include those for self, students, and / or patients. Psychotropic drugs affect neurons and neurotransmitters (NTs). Figure 1 provides a relatively detailed schema of presynaptic and postsynaptic neurons and the synapse that separates them. A careful review of this schema and the subsequent discussion of NTs will advance your understanding of psychopharmacology. In order to move toward a conceptual understanding of psychopharmacology, it important to consider three neuronal phenomena; polarization, action potentials, and ion channels. [FIGURE 1 OMITTED] Polarization, Action Potentials, and Ion Channels Polarization, Neurons fire or do not fire, depolarize or do not depolarize. Note the location of the "+" and "-" signs along the axons. These signs represent polar opposites on an electrical gradient similar to the poles of a flashlight battery. All or almost all, the "+" signs on the exterior of the cell membrane and all, or almost all, the "-" signs on the interior side of the cell membrane constitute a state of polarization (i.e., a resting state). Note also that on some locations of the axon a reversal of polarity exists, representing a localized depolarization event. During depolarization there is a marching effect, down the neuron from the cell body to the axonal terminal with a specific site of depolarization quickly repolarizing and so on, all occurring within milliseconds. Depolarization is said to be an all-or-nothing phenomenon--going full speed ahead or not going at all. Neurons hold an electrical charge at rest of, on average, -70 millivolts (mV). The voltage calculation is somewhat arbitrary, being based on the relative difference between extracellular and intracellular charges. Once the depolarizing march reaches the axonal terminal, [Ca.sup.++] channels open, allowing calcium to enter the terminal. [Ca.sup.++] facilitates two processes critical to neurotransmission: NT synthesis and NT release. More about this will be presented later. Action potentials. So far we have described the event of depolarization but not the how. Here we ask you to look closely at the receptors on the postsynaptic neurons. Receptors are located on the sodium channel. When an endogenous substance with affinity for these receptors binds to them, the sodium channel opens. The NTs and other agonists (i.e., drugs with both affinity for the receptor and ability to activate it) are referred to as ligands (ligandus, binding). These channels are referred to as ligand-gated channels. Figure 1 shows only a few of these receptors, where in reality there are thousands. When sufficient numbers of sodium channels are opened, allowing sodium to flow in, a significant change in polarity can occur, which, in turn, will trigger the opening of the more numerous voltage-gated channels located distally from the synapse on down to the axonal endings. …