Conformational restraint or rigidification is commonly used on a lead compound that is highly flexible and contains several rotatable single bonds. The more flexible a molecule, the more conformations it can adopt and the less chance there is of it being in the active conformation when it meets its target. Conformational restraint can be a useful strategy to try where the lead compound is a naturally occurring neurotransmitter in the body. Introducing an extra ring into the lead compound is often used to prevent single bond rotation. The extra ring is fused to an existing ring and includes bonds that were previously rotatable. Since these bonds are part of a ring system, they are no longer free to rotate and fewer conformations are possible. An alternative approach to conformational restraint is to introduce substituents that make certain conformations unlikely due to unfavorable steric interactions.