Serotonin 5-HT2A receptor binding in platelets from healthy subjects as studied by [3H]-lysergic acid diethylamide ([3H]-LSD): intra- and interindividual variability.
In studies on platelet 5-HT2A receptor binding in patients with neuropsychiatric disorders, there has been a marked variability and a considerable overlap of values between patients and controls. The causes of the large variability in 5-HT2A receptor parameters is still unsettled. In the present study, we have quantified the intra- and interindividual variability of platelet 5-HT2A receptor binding in 112 healthy subjects and explored factors that may influence 5-HT2A receptor binding, using [3H]-lysergic acid diethylamide as radioligand. Age, gender, blood pressure, and metabolic capacity of the liver enzymes CYP2D6 and CYP2C19 did not influence Bmax and Kd values. Body weight and body mass index (BMI) showed a negative correlation with Kd (p = .04 and .03, respectively), but not with Bmax. Bmax was significantly lower in the light half of the year than in the dark half of the year (p = .001), and Kd was significantly lower in the fall than in the summer and winter (p < .001). In females, there was a significant increase in Bmax from week 1 to week 2 of the menstrual cycle (p = .03). Females taking contraceptive pills had significantly higher Kd than drug-free females in weeks 1 and 4 of the menstrual cycle (p = .04). This study shows that a number of factors should be taken into account when using platelet 5-HT2A receptor binding in studies of neuropsychiatric disorders.
Spigset
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Division of Clinical Pharmacology, Norrland University Hospital, Umeå, Sweden.
Mjörndal
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008238:Lysergic Acid Diethylamide / Q000097:blood* / Q000493:pharmacokinetics; D008297:Male; D008597:Menstrual Cycle / Q000378:metabolism; D008875:Middle Aged; D011985:Receptors, Serotonin / Q000378:metabolism*; D012621:Seasons; D012702:Serotonin Antagonists / Q000097:blood* / Q000493:pharmacokinetics; D017366:Serotonin Receptor Agonists / Q000097:blood* / Q000493:pharmacokinetics; D012727:Sex Characteristics
D003278:Contraceptives, Oral, Hormonal; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D008238:Lysergic Acid Diethylamide