Posted by Pluto on June 6, 2004, at 3:18:32
In reply to Re: Anyone tried Anafranil, posted by Keith Talent on June 4, 2004, at 10:56:50
Hi Keith,
>What does this mean? Do you mean that these drugs mainly work by inhibiting noradrenaline reuptake? Or that they have alpha-1 receptor antagonism as a side effect?
Nortriptyline and desipramine, both works by inhibiting noradrenaline rather than the other main neurotransmitter involved in the case of depression that is serotonin. Yes, they both have effects on alpha receptor too, that may be the cause of high incidence of erectile difficulties attributed to these drugs. Reboxetine, a specific noradrenaline reuptake inhibitor has more pronounced action on erction even at lower doses. Alpha 2 antagonism usually leads to better erections in man and in extreme cases priapism can occur. Almost all alpha 2 antagonists have priapism as a side effect, though this drug induced priapism doesn't usually lead to permenant sexual dysfunction. (Trazodone is an exception, which can cause treatment resistant priapism and consequently permenant erectile dysfunction).
>Again, what does that mean? Blocking the serotonin transporter? Blocking serotonin-2 receptors? In point of fact, clomipramine is an extremely potent serotonin reuptake inhibitor and a moderately potent noradrenaline reuptake inhibitor. Its active metabolite, desmethylclomipramine, is an extremely potent noradrenaline reuptake inhibitor (about as powerful as desipramine at this). After steady-state concentrations of both clomipramine and its desmethyl- metabolite have been reached (about a week or two), the concentration of the desmethylclomipramine is substantially higher. Therefore, it is misleading to state, as you did, that "clomipramine mainly targets serotonin".
Clomipramine's high affinity on serotonin is doubtlessly proved and it is this preciousness that makes it the most effective anti-OCD medication. This doesn't mean it doesn't possess other properties too. Remember sertraline is a selective serotonin re-uptake inhibitor, but has pronounced dopaminergic actions too at doses higher than 100mg, but still we rate sertraline as a serotonin re-uptake inhibitor. Clomipramine's affinity on noradrenaline is the reason for it's use in narcolepsy. But it's main indication is OCD, not narcolepsy.>They cause vasodilation on the arterial side, which will lead to, not ameliorate, (reflex) tachycardia! Also, you forgot to mention that tricyclic-induced tachycardia is in large part due to muscarinic acetylcholine receptor antagonism (reducing the parasympathetic influence on the heart, and altering the balance in favour of sympathetic input to the heart).
Peripheral vasodilation on both resistance vessels and capacitance vessels does not provoke reflex tachycardia, but can be beneficial in some cases of tachycardia. (Check the data sheets of both drugs in ABPI Medicines compendium)
Best of luck. Please correct me, if I am wrong.
PLS
poster:Pluto
thread:353222
URL: http://www.dr-bob.org/babble/20040602/msgs/354201.html