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Re: Inderal-vs-Pindolol » JohnX

Posted by SLS on April 16, 2001, at 0:23:54

In reply to Re: Inderal-vs-Pindolol » SLS, posted by JohnX on April 15, 2001, at 22:21:10


> > Both pindolol (Visken) and propanolol (Inderal) antagonize (block) NE beta receptors. It is this action that is responsible for their therapeutic effects in cardiovasculature conditions. However, the property of pindolol that is thought to be most involved in its proposed antidepressant action is the antagonism of serotonergic 5-HT alpha-1a autoreceptors, a receptor that is not affected by propanolol. The antagonism of these autoreceptors actually increases the sensitivity and firing rate of serotonergic neurons. The two drugs are best not thought of as being interchangeable when used for depressions.


> Propranolol from what I have seen also has an antagonist effect on the serotonin 5ht-1a receptor. However, it has not been shown to have much of an anti-depressant benefit. Many markers of anti-depressant action are down-regulation of beta-adrenoreceptor. Propranolol being a full beta blocker actually has a potential side effect of inducing depression as it potently blocks the beta-adrenoreceptor. Pindolol is a partial antagonist (or agonist, which ever way you look at it). So I suspect this is part of the reason that it does not induce depression and the 5ht action is anti-depressant. Any thoughts?


Thanks for the correction, John.

I was surprised to see propanolol listed as a 5-HT1a antagonist, as I have not seen this mentioned in the literature I have come across. Pindolol seems to be the drug more often chosen as the probe in experiments. When I looked specifically for studies for which propanolol was used, it seemed to be considered as being very close to pindolol in potency.

You are quite a bit more familiar with the relative actions of these drugs on NE beta receptors than am I. A possibly important consideration in comparing the antidepressant effects of pindolol versus propanolol is that pindolol seems to show a higher affinity as an antagonist of presynaptic 5-HT1b autoreceptors. This action would act synergistically with its 5-HT1a antagonism to promote an increase in serotonergic neurotransmission. Perhaps, as you have stated, pindolol is only a partial antagonist at NE beta receptors, it might be less depressogenic than propanolol (I believe that notion that propanolol is depressogenic is still a point of debate). Thus, it is conceivable that the antidepressant effects of pindolol mediated through 5-HT1a/b antagonism predominate over a reduced depressogenic potential. Conversely, the relative lack of 5-HT1b antagonism by propanolol, coupled with its more potent NE beta antagonism, yields a net neutral or depressogenic result.

Thanks for motivating me to look into it. The thoughts I offered here seem too simplistic to me, and something seems to be missing. I’ll let you fill in the blanks.

:-)


- Scott

 

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