This chapter provides some of the issues concerning the experimental approach to the assessment of the pharmacodynamic effects of beta agonists, concentrating particularly on assessment of selectivity. Selectivity of beta agonists is defined in terms of relativity to the effects of isoprenaline, a nonselective agonist at beta receptors. It has stimulatory activity at both receptor types for any dose. An agonist selective at the beta2 receptor would stimulate that receptor with little or no effect at the beta1 receptor. Much of the original work investigating the pharmacological effects of beta agonists were performed before ligand-binding studies to beta1 and beta2 receptors were established; thus, definitions of selectivity may have been inaccurate. In vitro studies were receptor directed in that they used tracheal relaxation as an indicator of beta2 receptor activation, whereas increase in heart rate and contractility were thought to represent beta1 receptor stimulation.
Journal Article A pilot study of nicotine delivery to smokers from a metered-dose inhaler Get access Brent Caldwell, Brent Caldwell Search for other works by this author on: Oxford Academic PubMed Google Scholar Stuart Dickson, Stuart Dickson Search for other works by this author on: Oxford Academic PubMed Google Scholar Carl Burgess, Carl Burgess Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert Siebers, Robert Siebers Search for other works by this author on: Oxford Academic PubMed Google Scholar Sima Mala, Sima Mala Search for other works by this author on: Oxford Academic PubMed Google Scholar Adrienne Parkes, Adrienne Parkes Search for other works by this author on: Oxford Academic PubMed Google Scholar Julian Crane Julian Crane Search for other works by this author on: Oxford Academic PubMed Google Scholar Nicotine & Tobacco Research, Volume 11, Issue 4, April 2009, Pages 342–347, https://doi.org/10.1093/ntr/ntp027 Published: 03 April 2009 Article history Received: 04 October 2007 Accepted: 27 November 2008 Published: 03 April 2009
The hemodynamic effects of trazodone (150 mg) and Imipramine (75 mg) were examined in eight healthy subjects. Trazodone significantly increased left ventricular ejection time 1 (LVETI), but decreased both preejection period (PEP) and PEP/LVET ratio. It also decreased heart rate and systolic and diastolic blood pressure at 90 min after dosing. Imipramine initially increased total electromechanical systole I (QS2I) and PEP (30 min, P < 0.01), but at 150 and 180 min after dosing QS2I was significantly lower. Imipramine increased diastolic blood pressure at 30 min (P < 0.05) and increased systolic blood pressure between 90 and 180 min (P < 0.05). At 30 and 60 min heart rate was significantly depressed by imipramine. There were no significant changes in the values of stroke volume and cardiac output. These results suggest that trazodone has its major effect on the circulation through its alpha-receptor blocking activity, whereas the effects of imipramine are probably mediated through its ability to block reuptake of norepinephrine. Clinical Pharmacology and Therapeutics (1982) 32, 497–502; doi:10.1038/clpt.1982.194
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
'/%3e%3cuse xlink:href='%23a' transform='rotate(72 0 0)'/%3e%3cuse xlink:href='%23a' transform='rotate(-72 0 0)'/%3e%3cuse xlink:href='%23a' transform='scale(-1 1) rotate(72)'/%3e%3c/g%3e%3c/defs%3e%3cpath fill='%23012169' d='M0 0h1200v600H0z'/%3e%3cpath stroke='%23FFF' stroke-width='60' d='m0 0 600 300M0 300 600 0' clip-path='url(%23b)'/%3e%3cpath stroke='%23C8102E' stroke-width='40' d='m0 0 600 300M0 300 600 0' clip-path='url(%23c)'/%3e%3cpath stroke='%23FFF' stroke-width='100' d='M300 0v300M0 150h600' clip-path='url(%23b)'/%3e%3cpath stroke='%23C8102E' stroke-width='60' d='M300 0v300M0 150h600' clip-path='url(%23b)'/%3e%3cuse xlink:href='%23d' fill='%23FFF' transform='matrix(45.4 0 0 45.4 900 120)'/%3e%3cuse xlink:href='%23d' fill='%23C8102E' transform='matrix(30 0 0 30 900 120)'/%3e%3cg transform='rotate(82 900 240)'%3e%3cuse xlink:href='%23d' fill='%23FFF' transform='rotate(-82 519.022 -457.666) scale(40.4)'/%3e%3cuse xlink:href='%23d' fill='%23C8102E' transform='rotate(-82 519.022 -457.666) scale(25)'/%3e%3c/g%3e%3cg transform='rotate(82 900 240)'%3e%3cuse xlink:href='%23d' fill='%23FFF' transform='rotate(-82 668.57 -327.666) scale(45.4)'/%3e%3cuse xlink:href='%23d' fill='%23C8102E' transform='rotate(-82 668.57 -327.666) scale(30)'/%3e%3c/g%3e%3cuse xlink:href='%23d' fill='%23FFF' transform='matrix(50.4 0 0 50.4 900 480)'/%3e%3cuse xlink:href='%23d' fill='%23C8102E' transform='matrix(35 0 0 35 900 480)'/%3e%3c/svg%3e)
