Final answer:
Norepinephrine does not cross cell membranes well because it is polar and requires transport mechanisms. Its low permeability and oral bioavailability are confirmed through in vitro models like Caco-2 cells, which determine the Papp, and it's also subject to enzymatic degradation.
Step-by-step explanation:
Norepinephrine (often referred to as norepi) is a neurotransmitter that is not very permeable across cell membranes because it is a polar molecule, which means it does not cross lipid bilayers easily. The permeability of different substances across biological membranes is a function of their physiochemical properties, particularly their polarity. Molecules that are polar or charged typically require transport mechanisms to cross membranes, such as transporters or channels. In the central nervous system, neurotransmitters like norepinephrine are generally released into the synaptic cleft and do not need to cross the cell membrane to exert their function. However, their reuptake and clearance from the synaptic cleft often involve specific transporters.
According to studies such as those by Stewart et al. (1995), the permeability of substances can be assessed using cell monolayer models such as Caco-2 cells, which are used as an in vitro model of the human intestinal barrier. This testing can indicate whether a compound is likely to be easily absorbed when taken orally, through an apparent permeability coefficient (Papp). Norepinephrine is not known for high oral bioavailability, in part due to its poor membrane permeability and also because it is a substrate for enzymes like monoamine oxidase (MAO) and transporters like the organic cation transporter, which may limit its absorption and distribution when taken orally.