Ignite Creation Date:
2024-05-05 @ 11:24 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00029627
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2002-01-16
Brief Title:
Brain Receptors in Sympathetic Nervous System Regulation
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Alpha2-Adrenoreceptor AR Subtype Polymorphisms and Physiological Responses to Alpha2-AR Agonist and Antagonist Drugs
Status:
COMPLETED
Status Verified Date:
2004-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to investigate the role of brain receptors called alpha2-adrenoreceptors in regulating the sympathetic nervous system which maintains the supply of blood and fuel to the bodys organs in times of stress fear anger or exercise
Alpha2-adrenergic receptors alpha2-AR play a role in a variety of physiological functions There are three subtypes of alpha2-ARs and their differences are unknown This study will examine the functional roles of these three subtypes by comparing the behavioral biochemical psychophysiological and autonomic function effects of the alpha2-AR drugs clonidine and yohimbine
Participants in this study will undergo a physical examination electrocardiogram ECG and blood urine and saliva tests Women will have hormone tests to determine the time of their last period and the time of their next ovulation Participants will undergo neuropsychological testing and other procedures
Alpha2-adrenergic receptors alpha2-AR play a role in a variety of physiological functions There are three subtypes of alpha2-ARs and their differences are unknown This study will examine the functional roles of these three subtypes by comparing the behavioral biochemical psychophysiological and autonomic function effects of the alpha2-AR drugs clonidine and yohimbine
Participants in this study will undergo a physical examination electrocardiogram ECG and blood urine and saliva tests Women will have hormone tests to determine the time of their last period and the time of their next ovulation Participants will undergo neuropsychological testing and other procedures
Detailed Description:
Alpha2-adrenergic receptors alpha2-AR are cell surface receptors for catecholamines that bind to the GiG0 family of G proteins Alpha2-ARs are widely distributed in the central and peripheral nervous system and are known to play an important role in the regulation of catecholamine release This mechanism and the broad distribution of these receptors explain their role in a wide variety of physiological functions Alpha2-AR mediate central hypotensive sedative anesthetic and analgesic responses to alpha2-AR agonists However cardiovascular and other responses to the alpha2-AR agonists are subject to interindividual variation in the human population Such variability may be explained by genetic variation in the structure of the receptors themselves the cognate G proteins the transductional effectors or the downstream intracellular targets Molecular and pharmacological research has defined three alpha2-ARs subtypes designated alpha2A alpha2B and alpha2C All three alpha2-AR subtypes are involved in the regulation of blood pressure and these receptors also modulate sedation analgesia regulation of insulin release renal function cognition and behavior Biochemical research has identified three human genes that uniquely encode these alpha2-ARs Recently in preclinical studies polymorphisms of all three alpha2-AR subtypes have been described The three polymorphisms are each relatively abundant and two appear to be functional in vitro However in humans the in vivo physiological effect of these polymorphisms is unknown
This study will elucidate the potential functional role of the three alpha2-AR subtypes in humans by comparing the behavioral biochemical psychophysiological and autonomic function effects of the well-established alpha2-AR agonists and antagonists clonidine and yohimbine respectively in individuals selected for particular alpha2-AR genotypes Based on preclinical studies the following hypotheses will be tested 1 subjects homozygous or heterozygous for the alpha2A-AR Asn251Lys substitution will show a potentiation of clonidine-induced effects relative to subjects who have the Asn251Asn251 genotype and a reduction of yohimbine-induced effects 2 subjects homozygous or heterozygous for a alpha2B-AR three glutamic acid deletion residues 301-303 will show reduced effects of the alpha2-AR agonist clonidine and possibly a potentiation of effects of yohimbine and 3 we will evaluate whether altered responses in either direction occur in subjects homozygous and heterozygous for an in-frame deletion of a alpha2C-AR homologous repeat occurring at codons 322-325 relative to subjects without this deletion allele
This study will elucidate the potential functional role of the three alpha2-AR subtypes in humans by comparing the behavioral biochemical psychophysiological and autonomic function effects of the well-established alpha2-AR agonists and antagonists clonidine and yohimbine respectively in individuals selected for particular alpha2-AR genotypes Based on preclinical studies the following hypotheses will be tested 1 subjects homozygous or heterozygous for the alpha2A-AR Asn251Lys substitution will show a potentiation of clonidine-induced effects relative to subjects who have the Asn251Asn251 genotype and a reduction of yohimbine-induced effects 2 subjects homozygous or heterozygous for a alpha2B-AR three glutamic acid deletion residues 301-303 will show reduced effects of the alpha2-AR agonist clonidine and possibly a potentiation of effects of yohimbine and 3 we will evaluate whether altered responses in either direction occur in subjects homozygous and heterozygous for an in-frame deletion of a alpha2C-AR homologous repeat occurring at codons 322-325 relative to subjects without this deletion allele
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 02-M-0089 | None | None | None |