Re: RLS-Doxepin & sleep does it work?

[Guest guest]

Cindy,

Have you gotten very little sleep the last six days because of RLS Symptoms?

Doexpin is tricyclic antidepressant and all of that group are notorious for

making RLS symptoms worse; they interfer with the uptake of D-2 dopamine

receptor is probably why. It is thought many RLS patients are lacking in

dopamine; interfer with a dopamine receptor to take up what there is and you

are in trouble!

I went and did a Medline or search of the medical literature. Although I

could find nothing on Doxepin and RLS, I did find the below which are very

technical, granted.

Hope this helps!

Barbara

Binding of antidepressants to human brain receptors: focus on newer

generation compounds.

Author: Cusack B; A; Richelson E

Address: Department of Research, Mayo Clinic ville, FL 32224.

Source: Psychopharmacology (Berl), 1994 May, 114:4, 559-65

Abstract: Using radioligand binding assays and post-mortem normal human brain

tissue, we obtained equilibrium dissociation constants (Kds) for 17

antidepressants and two of their metabolites at histamine H1, muscarinic,

alpha 1-adrenergic, alpha 2-adrenergic, dopamine D2, serotonin 5-HT1A, and

serotonin 5-HT2 receptors. Several newer antidepressants were compared with

older drugs. In addition, we studied some antimuscarinic, antiparkinson,

antihistamine, and neuroleptic compounds at some of these receptors. For the

antidepressants, classical tricyclic antidepressants were the most potent

drugs at five of the seven receptors (all but alpha 2-adrenergic and 5-HT1A

receptors).

The chlorophenylpiperazine derivative antidepressants (etoperidone,

nefazodone, trazodone) were the most potent antidepressants at alpha

2-adrenergic and 5-HT1A receptors. Of ten antihistamines tested, none was

more potent than doxepin at histamine H1 receptors. At muscarinic receptors

antidepressants and antihistamines had a range of potencies, which were

mostly weaker than those for antimuscarinics. From the in vitro data, we

expect adinazolam, bupropion, fluoxetine, sertraline, tomoxetine, and

venlafaxine not to block any of these five receptors in vivo. An

antidepressant's potency for blocking a specific receptor is predictive of

certain side effects and drug-drug interactions. These studies can provide

guidelines for the clinician in the choice of antidepressant.

Brain 5-HT1C receptors and antidepressants.

Author: Jenck F; Moreau JL; Mutel V; JR

Address: Pharma Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Source: Prog Neuropsychopharmacol Biol Psychiatry, 1994 May, 18:3, 563-74

Abstract: A variety of antidepressants of different chemical classes were

tested for their in vivo and in vitro activity at 5-HT1C receptors in the

brain. Conventional tricyclic antidepressants (imipramine, desipramine,

maprotiline, clomipramine, trimipramine, amitriptyline, nortriptyline,

doxepin, amoxapine, oxaprotiline) and two atypical antidepressants (mianserin

and trazodone) were found to display affinity for 5-HT1C receptors in the

nanomolar range.

Antidepressants of other chemical classes and mechanisms of action

(serotonin uptake inhibitors: fluoxetine, citalopram, sertraline,

fluvoxamine; noradrenaline-dopamine uptake inhibitors: nomifensine,

bupropion, amineptine; or monoamine oxidase inhibitors: moclobemide,

iproniazid) had affinities in the micromolar range for 5-HT1C receptors,

except fluoxetine. When tested in an in vivo functional model revealing

agonistic or antagonistic properties at 5-HT1C receptors, all antidepressants

displaying high affinity for this receptor type (except fluoxetine,

clomipramine, trimipramine and oxaprotiline) were antagonists at 5-HT1C

receptors.

Antidepressants with lower 5-HT1C receptor affinity (except

nomifensine) were inactive in this functional in vivo model. Antagonism at

brain 5-HT1C receptors is a component of the antiserotonergic properties of a

number of established antidepressants, especially of the tricyclic class.

Fluoxetine and two other serotonin uptake inhibitors without affinity for

neuronal receptors.

Author: Wong DT; Bymaster FP; Reid LR; Threlkeld PG

Source: Biochem Pharmacol, 1983 Apr, 32:7, 1287-93

Abstract: Fluoxetine and nine other antidepressant drugs which interact with

brain receptors for neurotransmitters were studied in vitro using

radioligand-binding techniques and transmitter-coupled adenylate cyclase

assays. Tricyclic antidepressant drugs (desipramine, imipramine,

clomipramine, amitriptyline and doxepin) had marked affinity for

alpha-adrenergic, muscarinic cholinergic and histaminergic H1 receptors, and

lesser affinity for serotonin and dopamine receptors.

Mianserin was relatively similar to some of the tricyclic compounds,

whereas trazodone had less affinity for most receptors except serotonin and

alpha-adrenergic receptors. Fluoxetine had little affinity for any of these

receptors, and the same was true for zimelidine and fluvoxamine, two other

selective inhibitors of serotonin uptake. None of the compounds showed much

affinity for beta-adrenergic receptors, opiate receptors, gamma-aminobutyric

acid receptors, or benzodiazepine receptors. The present findings with

fluoxetine are consistent with the virtual absence of anticholinergic or

other side effects often observed with tricyclic antidepressant drugs in

animal models or during the treatment of depressed patients.