Nicotinic Agonist - Drug Design

Drug Design

Drugs that influence nAChRs can be agonists, partial agonists or antagonists. Agonists, e.g. nicotine, can however act as depolarizing agents when encountered to nAChRs for some time (seconds or minutes, depending on concentration and nAChR subtype), chronic exposure to agonist can also lead to long lasting functional deactivation because of rapid and persistent desensitization. Partial nAChR agonists have been studied since they seem to be helpful in smoking cessation. The partial agonists are believed to bind to the nAChRs and stimulate the release of dopamine in smaller portions than the agonists and therefore compensate for the absence of nicotine.
The lack of specificity among some of the nicotinic agonists is well known and is a potential problem when using them to treat illnesses that require targeting a specific subtype of nAChRs. Among these nonspecific agonists are for example ACh, nicotine and epibatidine that all target more than one subtype of nAChRs.