There are several different types of partial agonists. These drugs maintain their pharmaceutical action by binding to a specific receptor and causing weak action that is both agonistic and antagonistic in nature. Partial agonists cause varied, but specific, physiologic effects, which are based on which receptor type they have an affinity for. Some common conditions for which partial agonists are prescribed include schizophrenia, opiate addiction, and hypertension. Some well-known drugs belonging to this category are buspirone, aripiprazole, and pindolol.
A partial agonist can be thought of as a reasonable, but less than perfect, fit for its corresponding receptor. As it binds, it fills the receptor and, in effect, blocks the receptor from being open to any other substance or ligand. It does not bind totally, however, and cannot cause enough of a change within the receptor to facilitate a maximum response. It causes an agonistic effect because a signal, although it is weaker in nature than one caused by a full agonist, is sent. On the other hand, it causes an antagonistic effect by totally blocking the effect of a substance or ligand that might be competing for the receptor site.
Partial agonists are used often in the treatment of opiate addiction and withdrawal. Chronic opiate users inevitably develop a high tolerance to opioid medication. This happens because the brain responds to regular saturation at the opiate receptor site by growing more receptors, which then need to be filled in order for the user to feel the drug’s effects. It becomes impossible for the user to fill all of the receptor sites and, at this point, he or she will experience painful withdrawal. Buspirone works by partially binding to the opiate receptors, which mitigate the withdrawal symptoms without producing a euphoric high.
Aripiprazole, another partial agonist drug, is used to treat schizophrenia by way of the dopamine 2 (D2) receptor. More traditional anti-psychotic medication works by completely blocking the D2 site, which causes a cessation of positive schizophrenic symptoms like hallucinations and delusions. Completely blocking the D2 receptor, however, can cause patients to lose the ability to feel pleasure—called anhedonia—, become depressed, or suffer the exacerbation of the negative symptoms of schizophrenia. These unwanted side effects can be mitigated by using drugs like aripiprazole instead of full agonists because they bind to the receptor site in a weaker way and, in effect, let enough dopamine activation take place to ward off negative reactions.
