Abstract
The present experiments were undertaken to ascertain whether non-tricyclic, clinically effective, antidepressant drugs such as the tetracyclic mianserin and the serotonin uptake inhibitor, zimelidine, cause alterations of central noradrenergic receptor systems similar to those elicited by classical tricyclic antidepressants, MAO inhibitors and ECT. Like desipramine (DMI), mianserin and zimelidine caused, after chronic administration, a significant reduction in the sensitivity of the cyclic AMP response to (R)-norepinephrine while a single dose of the drugs did not affect the neurohormonal response. The basal levels of the nucleotide were not changed by the antidepressant drugs following acute or chronic administration. While the noradrenergic subsensitivity caused by DMI was linked to a reduction in the B(max) value of 3H-dihydroalprenolol binding, the subsensitivity caused by mianserin and zimelidine was not associated with a decreased density of β-adrenergic receptors. In accord with these data on β-adrenergic receptor binding, the responsiveness of the adrenergic cyclic AMP generating system to the β-adrenergic agonist, (R)-isoproterenol, was significantly reduced following chronic treatment with DMI but not with mianserin or zimelidine. The results provide further evidence for the theory that the delayed therapeutic action of different prototypes of antidepressant treatments may be related to the delayed change in noradrenergic receptor function and that a reduction in the density of β-adrenergic receptors is only one mechanism by which the sensitivity of the system is regulated.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 983-987 |
| Number of pages | 5 |
| Journal | Neuropharmacology |
| Volume | 19 |
| Issue number | 10 |
| DOIs | |
| State | Published - 1980 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Drug Discovery
- Pharmacology
Cite this
Action of mianserin and zimelidine on the norepinephrine receptor coupled adenylate cyclase system in brain : Subsensitivity without reduction in β-adrenergic receptor binding. / Mishra, R.; Janowsky, Aaron; Sulser, F.
In: Neuropharmacology, Vol. 19, No. 10, 1980, p. 983-987.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Action of mianserin and zimelidine on the norepinephrine receptor coupled adenylate cyclase system in brain
T2 - Subsensitivity without reduction in β-adrenergic receptor binding
AU - Mishra, R.
AU - Janowsky, Aaron
AU - Sulser, F.
PY - 1980
Y1 - 1980
N2 - The present experiments were undertaken to ascertain whether non-tricyclic, clinically effective, antidepressant drugs such as the tetracyclic mianserin and the serotonin uptake inhibitor, zimelidine, cause alterations of central noradrenergic receptor systems similar to those elicited by classical tricyclic antidepressants, MAO inhibitors and ECT. Like desipramine (DMI), mianserin and zimelidine caused, after chronic administration, a significant reduction in the sensitivity of the cyclic AMP response to (R)-norepinephrine while a single dose of the drugs did not affect the neurohormonal response. The basal levels of the nucleotide were not changed by the antidepressant drugs following acute or chronic administration. While the noradrenergic subsensitivity caused by DMI was linked to a reduction in the B(max) value of 3H-dihydroalprenolol binding, the subsensitivity caused by mianserin and zimelidine was not associated with a decreased density of β-adrenergic receptors. In accord with these data on β-adrenergic receptor binding, the responsiveness of the adrenergic cyclic AMP generating system to the β-adrenergic agonist, (R)-isoproterenol, was significantly reduced following chronic treatment with DMI but not with mianserin or zimelidine. The results provide further evidence for the theory that the delayed therapeutic action of different prototypes of antidepressant treatments may be related to the delayed change in noradrenergic receptor function and that a reduction in the density of β-adrenergic receptors is only one mechanism by which the sensitivity of the system is regulated.
AB - The present experiments were undertaken to ascertain whether non-tricyclic, clinically effective, antidepressant drugs such as the tetracyclic mianserin and the serotonin uptake inhibitor, zimelidine, cause alterations of central noradrenergic receptor systems similar to those elicited by classical tricyclic antidepressants, MAO inhibitors and ECT. Like desipramine (DMI), mianserin and zimelidine caused, after chronic administration, a significant reduction in the sensitivity of the cyclic AMP response to (R)-norepinephrine while a single dose of the drugs did not affect the neurohormonal response. The basal levels of the nucleotide were not changed by the antidepressant drugs following acute or chronic administration. While the noradrenergic subsensitivity caused by DMI was linked to a reduction in the B(max) value of 3H-dihydroalprenolol binding, the subsensitivity caused by mianserin and zimelidine was not associated with a decreased density of β-adrenergic receptors. In accord with these data on β-adrenergic receptor binding, the responsiveness of the adrenergic cyclic AMP generating system to the β-adrenergic agonist, (R)-isoproterenol, was significantly reduced following chronic treatment with DMI but not with mianserin or zimelidine. The results provide further evidence for the theory that the delayed therapeutic action of different prototypes of antidepressant treatments may be related to the delayed change in noradrenergic receptor function and that a reduction in the density of β-adrenergic receptors is only one mechanism by which the sensitivity of the system is regulated.
UR - http://www.scopus.com/inward/record.url?scp=0018879591&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0018879591&partnerID=8YFLogxK
U2 - 10.1016/0028-3908(80)90009-X
DO - 10.1016/0028-3908(80)90009-X
M3 - Article
C2 - 6252500
AN - SCOPUS:0018879591
VL - 19
SP - 983
EP - 987
JO - Neuropharmacology
JF - Neuropharmacology
SN - 0028-3908
IS - 10
ER -