title: Acute and chronic idazoxan in normal volunteers: biochemical, physiological and psychological effects.
abstract: The acute and chronic effects of the selective a(2)-antagonist idazoxan were studied in 12 normal volunteers. Plasma 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), blood pressure and psychological responses to oral challenge doses of idazoxan 40 mg were measured twice, on the first and 22nd day of treatment with idazoxan 40 mg t.d.s. Changes in nocturnal melatonin output were studied on six occasions, before, during and after idazoxan treatment. Although baseline MHPG levels were significantly reduced after chronic treatment with idazoxan, idazoxan challenge did not alter MHPG concentrations on either test day. A small rise in systolic blood pressure occurred after acute but not chronic idazoxan challenge tests. Systolic blood pressure values were significantly lower during the chronic compared with the acute test. Diastolic blood pressure and heart rate were not affected by acute or chronic treatment. Subjects reported increases in self- ratings of arousal and reductions in sedation and anxiety of similar magnitude after acute and chronic idazoxan. Nocturnal plasma melatonin secretion was not altered by drug administration or withdrawal, although urinary 6-sulphatoxymelatonin excretion was significantly reduced on acute withdrawal. The increase in systolic blood pressure and arousal self-ratings after acute idazoxan are in accordance with the reported effects of other a(2)-antagonists, although we did not find increased anxiety or elevated plasma MHPG levels. Chronic idazoxan appears to reduce or normalize activity of noradrenergic systems, indicated by reduced baseline systolic blood pressure and MHPG, and loss of the pressor response to idazoxan. Withdrawal of idazoxan leads to an abrupt fall in noradrenergic activity, as demonstrated by the fall in urinary 6-sulphatoxymelatonin.
authors.affiliation: Reckitt and Colman Psychopharmacology Unit, School of Medical Sciences, Bristol.
authors.forename: P
authors.initials: P
authors.lastname: Glue
authors.forename: S
authors.initials: S
authors.lastname: Wilson
authors.forename: C
authors.initials: C
authors.lastname: Lawson
authors.forename: G M
authors.initials: GM
authors.lastname: Campling
authors.forename: M
authors.initials: M
authors.lastname: Franklin
authors.forename: P J
authors.initials: PJ
authors.lastname: Cowen
authors.forename: D J
authors.initials: DJ
authors.lastname: Nutt