PMID: 9190859Jun 1, 1997Paper

Pharmacodynamics of acute tolerance to multiple nicotinic effects in humans

The Journal of Pharmacology and Experimental Therapeutics
K FattingerN L Benowitz

Abstract

Tolerance is an important determinant of addiction as well as therapeutic and/or toxic effects of drugs. The development of acute tolerance to various effects of nicotine was studied in nine healthy smokers who were abstaining from tobacco. Nicotine was infused rapidly to reach a concentration of about 25 ng/ml, followed by a computer-controlled infusion to maintain that concentration. A novel semiparametric model of nicotine effects and tolerance was developed. Tolerance to various effects of nicotine (increases in heart rate, blood pressure, plasma epinephrine and energy expenditure) occurred within the range of nicotine levels found in smokers. However, the rate of tolerance development varied considerably. The half-lives of tolerance ranged from 3.5 min for the increase in energy expenditure to 70 min for systolic blood pressure. There was no apparent tolerance to the effects on free fatty acid concentrations, which reflects lipolysis. Differences in the pharmacodynamics of tolerance may reflect differences in rate of desensitization of various subtypes of nicotinic receptors and/or differences in mechanisms of tolerance for various nicotinic effects.

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.