The pharmacology of (-)-nicotine and novel cholinergic channel modulators.
Advances in the understanding of the molecular biology and pharmacology of nAChRs may provide targets for the development of novel and selective modulators of nAChRs in the brain. This contention is supported by the dissimilar behavioral effects observed following systemic administration of currently available nicotinic ligands. The concept of multiple subtypes of nAChRs is not unique, as evidenced by the pharmacology of other ligand-gated ion channels, such as GABA-A receptor, which also exist in multiple subtypes. At present, with respect to the nAChRs, relatively few of the subtypes identified have been cloned from human tissue and pharmacologically evaluated, but several groups are focusing their research efforts in this direction. With a thorough understanding of the pharmacological and functional characteristics of more of the putative human nAChR subtypes, this knowledge will facilitate the discovery of more efficacious and less toxic ChCMs that may provide potential novel therapeutic agents for a variety of CNS conditions.
Brioni
J D
JD
Abbott Laboratories, Abbott Park, Illinois 60064, USA.
Decker
M W
MW
Sullivan
J P
JP
Arneric
S P
SP
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001597:Benzylidene Compounds / Q000494:pharmacology; D001923:Brain Chemistry; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000737:chemistry / Q000502:physiology*; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000502:physiology*; D019966:Substance-Related Disorders
D014151:Anti-Anxiety Agents; D001597:Benzylidene Compounds; D018377:Neurotransmitter Agents; D018722:Nicotinic Agonists; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D009538:Nicotine