Binding of yohimbine and imipramine to platelets in depressive illness

Abstract

SynopsisRadioligand binding to intact platelets was carried out in antidepressant-free patients and the 1 mg dexamethasone suppression test (DST) was performed. There were no differences in binding characteristics between patients and controls for either [H]yohimbine or [H]imipramine. There were no differences in binding between patients classified as endogenous using the Newcastle Scale, compared with non-endogenous patients, and no difference between DST suppressors and non-suppressors. The severity of depression did not affect binding values. After 4–6 weeks antidepressant treatment [H]yohimbine binding was significantly reduced but [H]imipramine binding was unaffected.

Alpha-2-Adrenoreceptor Binding as a Possible Vulnerability Marker for Affective Disorders

“…The last criterion for a vulnerability marker remains to be demonstrated. Indeed, the state independence, which refers to the sta bility of the trait over time, regardless of the clinical sta tus, is unsettled in the present study and in the previous studies: Smith et al [1983], Cameron et al [1984], and Braddok et al [1986] found a lower Bmax after tricyclic treatment, whereas Stahl et al [1983], Campbell et al [1985], Wolfe et al [1989], and Katona [1989] could not replicate these results, when using 3H-yohimbine as a radioligand.…”

“…To date, only one study, using dihydroergocryptine, a nonspecific a-radioligand, had found a similar result [Wood and Coppen, 1983]. Most of the studies using 3H-yohimbine binding have not found any significant change in Bmax values between depressed pa tients and normals [Wolfe et al, 1987;Campbell et al, 1985;Stahl et al, 1983;Daiguji et al, 1981;Braddok et al, 1986;Cameron et al, 1984;Smith et al, 1983], How ever, a careful examination of the Bmax values in these studies shows a general, but not statistically significant trend toward lower values in depressed patients [Daiguji et al, 1981;Stahl et al, 1983;Campbell et al, 1985;Wolfe et al, 1987], Among the numerous methodologi cal variables which differ between studies, the selection of different patient populations has to be emphasized. Indeed, most of the studies did not separate unipolar from bipolar patients, except Daiguji et al [1981], who found a slightly higher Bmax in depressed bipolar patients than in unipolar patients, but the number of bipolar patients (n = 3) was very small.…”

“…The same differences between studies appear for the binding parameters after antidepressant drugs, lith ium or electroconvulsive therapy and clinical improve ment. Most of the studies using clonidine have found decreased Bmax values after antidepressant treatment [Garcia-Sevilla et al, 1981;Smith et al, 1983;Braddok et al, 1986], whereas most of the yohimbine or rauwolscine studies failed to reproduce these results [Stahl et al, 1983;Campbell et al, 1985;Pimoule et al, 1983;Wolfe et al 1989], except Smith et al [1983] in de pressed patients, and Cameron et al [1984] in panic anxious patients, who found a lower Bmax value after tri cyclic antidepressant treatment. However, other factors such as treatment length, type of drug, catecholamine blood level, clinical response, could interfere with the results [Piletz et al, 1986;Kafka and Paul, 1986], No effect of age, sex, exercise, severity and subtyping of depression has been demonstrated [Piletz et al, 1986], but a seasonal effect on the Kd of 3H-yohimbine binding has been reported [Katona et al, 1989], Thus, studies on platelet ci2-adrenoreceptors or binding in depressed pa tients are so far inconclusive.…”

Correlation between Platelet α₂-Adrenoreceptors and Symptom Severity in Major Depression

“…Similarly, with the binding of another · 2 -adrenergic antagonist, [ 3 H]yohimbine, there was no difference between depressed patients and control subjects [29][30][31], except in one study [32]. On the contrary, the binding of partial · 2 -adrenergic agonists, such as clonidine and paminoclonidine, revealed an increased density of the receptors in major depression [18,33]; however, it must be stressed that these compounds are not selective and bind with high affinity to imidazoline receptors [34] and with heterogeneous affinity to · 2 -adrenoreceptors.…”

Imipramine Binding as a Predictor of Fluoxetine Response in Depressed Patients

“…Some studies have shown a reduction either in the number of the carrier proteins for 5-HT [5][6][7] or in the number of 3H-IMI sites in depressed patients [8][9][10][11][12], although controversies exist [13][14][15][16][17], Such a reduction has been proposed as a biologi cal marker, either trait-or state-dependent, for depression [18][19][20]. However, subsequent replications of these find ings in different psychiatric conditions [for review, see 21] make the proposal of decreased 3H-IMI binding as a marker for depression no longer tenable.…”