Posted by Quintal on January 20, 2007, at 0:02:44
In reply to Re: Zoloft and dopamine reuptake inhibition, posted by halcyondaze on January 19, 2007, at 21:44:16
__________________________________________________
Using radioligand binding assays, we determined the equilibrium dissociation constants (KD's) for 37 antidepressants, three of their metabolites (desmethylcitalopram, desmethylsertraline, and norfluoxetine), some mood stabilizers, and assorted other compounds (some antiepileptics, Ca2+ channel antagonists, benzodiazepines, psychostimulants, antihistamines, and monoamines) for the human serotonin, norepinephrine, and dopamine transporters. Among the compounds that we tested, mazindol was the most potent at the human norepinephrine and dopamine transporters with KD's of 0.45 +/- 0.03 nM and 8.1 +/- 0.4 nM, respectively. Sertraline (KD = 25 +/- 2 nM) and nomifensine (56 +/- 3 nM) were the two most potent antidepressants at the human dopamine transporter. We showed significant correlations for antidepressant affinities at binding to serotonin (R = 0.93), norepinephrine (R = 0.97), and dopamine (R = 0.87) transporters in comparison to their respective values for inhibiting uptake of monoamines into rat brain synaptosomes.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9537821&dopt=Abstract
__________________________________________________
http://www.preskorn.com/columns/9907.htmlhttp://www.preskorn.com/books/ssri_s3.html
So it would seem sertraline is one of the most potent SDRIs by far among the newer antidepressants?
Yet:
__________________________________________________"In Table 3.3, results are shown for the inhibition of the dopamine uptake pump. None of the TCAs or the SSRIs have substantial action on this neurotransmitter pump. Although sertraline is consistently the most potent, it is still 100 times less potent in terms of inhibiting the dopamine versus the serotonin uptake pump. That means the physician would have to increase the dose (ie, the concentration) of sertraline 100 times higher than that needed to inhibit the serotonin uptake pump before a comparable effect would be achieved on the dopamine uptake pump. Thus, the ratios shown in the bottom of Table 3.3 can be misleading if not viewed within the context of the actual affinity of the drug for a secondary SOA relative to its affinity for its primary SOA and relative to the clinically relevant concentration needed to produce the desired clinical effect. Recall that citalopram and fluoxetine are marketed as racemates (see Section 2). The values shown in the above tables for uptake inhibition are for the racemates of these two SSRIs. Table 3.4 shows the value for the individual enantiomers of each of these SSRIs and their major metabolite."
__________________________________________________And this wonderful little table:
__________________________________________________TABLE 3.6 — Pharmacologic Properties of Antidepressants and Possible Clinical Consequences
Property Consequences
Blockade of histamine (H-1and H-2) receptors: Sedation, drowsiness; potentiation of central depressant drugs; weight gain
Blockade of muscarinic acetylcholine receptors: Dry mouth, blurred vision, sinus tachycardia, constipation, urinary retention, memory impairment
Blockade of norepinephrine uptake at nerve endings: Antidepressant efficacy (?); tremors, jitteriness; tachycardia; diaphoresis; blockade of the antihypertensive effects of guanethidine; augmentation of pressor effects of sympathomimetic amines; erectile and ejaculatory dysfunction
Blockade of serotonin uptake at nerve endings: Antidepressant efficacy (?); sexual dysfunction; nausea, vomiting, diarrhea; anorexia; increase or decrease in anxiety (dose-dependent); asthenia (tiredness); insomnia; extrapyramidal side effects; interactions with L-tryptophan, monoamine oxidase inhibitors, fenfluramine, and occasionally lithium
Blockade of serotonin-2 (5-HT2) receptors: Antidepressant efficacy (?), ejaculatory dysfunction, hypotension, alleviation of migraine headaches, decrease in anxiety (?), decrease motor restlessness (?)
Blockade of a1-adrenergic receptors: Postural hypotension, dizziness which predisposes to falls possibly resulting in broken bones and subdural hematomas, potentiation of antihypertensive drugs
Blockade of a2-adrenergic receptors: Priapism; blockade of the antihypertensive effects of clonidine, a-methyldopa, guanabenz, guanfacine
Blockade of fast sodium channels: Slow repolarization, delay intracardiac conduction, reduce some arrhythmias at low concentrations, cause arrhythmias, seizures at high concentrations
__________________________________________________
I wonder if taking sertraline with tianeptine would reduce the SSRI effect making it more tolerable at higher doses, enabling a stronger DA reuptake effect?Q
poster:Quintal
thread:724214
URL: http://www.dr-bob.org/babble/20070119/msgs/724295.html