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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 4 of 4. This is the beginning of the thread.
Posted by don_bristol on January 10, 2005, at 14:38:37
Does anyone know of the interaction between the anti-fungal medication Lamisil (terbinafine) and Parnate?
I have been taking 40 mg Parnate for a few months. Recently I had to take 250 mg of oral Lamisil for 6 weeks.
Maybe it was just a co-incidence but soon after I started taking the Lamisil I felt the Parnate was much "stronger" than usual. I was more wakeful and had trouble wanting to go to sleep as I was not feeling sleepy at nights. I would estimate that the effect was equivalent to something like an extra 10 to 15 mg Parnate.
(Also my regular sleeping medication 10mg Zolpidem i.e. Ambien seemed to be much more potent when I was on Lamisil. This time it seemed to double in strength.)
I am not sure it was merely co-incidence. But there is little info on Lamisil interactions with MAOIs. The most explicit I have found is this from http://www.healthdigest.org/TERBINAFINE-(Oral)-(Tablet)_6749_PRO.php
"Make sure your doctor knows if you are also using cimetidine .... , blood pressure medicine .... , an MAO inhibitor (Eldepryl, Marplan, Nardil, Parnate), or medicine for depression (amitriptyline, clomipramine, ....".
Can anyone who understands the chemistry say if the P450 enyzme system explains why Lamisil *seemed* to block the breakdown of Parnate?
It is said that Lamisil is a potent inhibitor of CYP2D6. I don't really understand this topic but I have read that Parnate is a potent inhibitor of CYP2A6 as well as having something to do with several other enzymes in the P450 system.
Does anyone have any further info on this topic?
Thank you for any information.
Don.
Posted by King Vultan on January 10, 2005, at 15:23:12
In reply to Is Parnate potentiated by Lamisil (anti-fungal)?, posted by don_bristol on January 10, 2005, at 14:38:37
> Does anyone know of the interaction between the anti-fungal medication Lamisil (terbinafine) and Parnate?
>
> I have been taking 40 mg Parnate for a few months. Recently I had to take 250 mg of oral Lamisil for 6 weeks.
>
> Maybe it was just a co-incidence but soon after I started taking the Lamisil I felt the Parnate was much "stronger" than usual. I was more wakeful and had trouble wanting to go to sleep as I was not feeling sleepy at nights. I would estimate that the effect was equivalent to something like an extra 10 to 15 mg Parnate.
>
> (Also my regular sleeping medication 10mg Zolpidem i.e. Ambien seemed to be much more potent when I was on Lamisil. This time it seemed to double in strength.)
>
> I am not sure it was merely co-incidence. But there is little info on Lamisil interactions with MAOIs. The most explicit I have found is this from http://www.healthdigest.org/TERBINAFINE-(Oral)-(Tablet)_6749_PRO.php
>
> "Make sure your doctor knows if you are also using cimetidine .... , blood pressure medicine .... , an MAO inhibitor (Eldepryl, Marplan, Nardil, Parnate), or medicine for depression (amitriptyline, clomipramine, ....".
>
> Can anyone who understands the chemistry say if the P450 enyzme system explains why Lamisil *seemed* to block the breakdown of Parnate?
>
> It is said that Lamisil is a potent inhibitor of CYP2D6. I don't really understand this topic but I have read that Parnate is a potent inhibitor of CYP2A6 as well as having something to do with several other enzymes in the P450 system.
>
> Does anyone have any further info on this topic?
>
> Thank you for any information.
>
> Don.
>
AFAIK, Parnate is not metabolized by the CYP-450 enzyme system in general or the 2D6 enzyme in particular. Rather, it is metabolized by the MAO enzyme system, of which it is a potent inhibitor, and from which its antidepressant properties are derived.Todd
Posted by Don_Bristol on January 11, 2005, at 16:49:13
In reply to Re: Is Parnate potentiated by Lamisil (anti-fungal)?, posted by King Vultan on January 10, 2005, at 15:23:12
> AFAIK, Parnate is not metabolized by the CYP-450
> enzyme system in general or the 2D6 enzyme in particular.
> Rather, it is metabolized by the MAO enzyme system,
> of which it is a potent inhibitor, and from which its
> antidepressant properties are derived.
>
> ToddTodd, I don't really understand all the subtleties of P450 but I have read the following which suggests Parnate may have some noticeable P450 activity:
"The results demonstrated that tranylcypromine is a
competitive inhibitor of CYP2C19 (Ki = 32 microM)
competitive inhibitor of CYP2D6 (Ki = 367 microM)
noncompetitive inhibitor of CYP2C9 (Ki = 56 microM).None of these inhibitory effects are considered clinically
significant at usual therapeutic doses. However, in high
dose tranylcypromine therapy, or in poor metabolizers
of CYP2C19 substrates, clinically significant interactions
might occur."And also somewhere on the Net I picked up this snippet:
"the effects of trans-(+/-)-2-phenylcyclopropylamine
(tranylcypromine), a potent CYP2A6 inhibitor, on human
liver microsomal cytochromes P450 (CYP) were studied
to elucidate its selectivity........ Potency and selectivity of tranylcypromine were
strongly dependent on the amine group,"And even this (whatever it means!!!):
"In human liver microsomes tranylcypromine induced type
II and cyclopropylbenzene type I difference spectrum.
According to the double reciprocal analysis of these
spectral responses both tranylcypromine and cyclopropyl
benzene may have at least two P450-related binding sites
in liver microsomes."It seems better agreed that, as I posted before, Lamisil is a potent inhibitor of CYP2D6.
Now what does all this mean? :-) Does it in any way help explain the fact that I had a strong "uplift" in the Parnate when I took Lamisil?
.
Posted by King Vultan on January 11, 2005, at 17:20:05
In reply to Do MAOIs make normal people high? » King Vultan, posted by Don_Bristol on January 11, 2005, at 16:49:13
>
>
>
> Todd, I don't really understand all the subtleties of P450 but I have read the following which suggests Parnate may have some noticeable P450 activity:
>
> "The results demonstrated that tranylcypromine is a
> competitive inhibitor of CYP2C19 (Ki = 32 microM)
> competitive inhibitor of CYP2D6 (Ki = 367 microM)
> noncompetitive inhibitor of CYP2C9 (Ki = 56 microM).
>
> None of these inhibitory effects are considered clinically
> significant at usual therapeutic doses. However, in high
> dose tranylcypromine therapy, or in poor metabolizers
> of CYP2C19 substrates, clinically significant interactions
> might occur."
>
> And also somewhere on the Net I picked up this snippet:
>
> "the effects of trans-(+/-)-2-phenylcyclopropylamine
> (tranylcypromine), a potent CYP2A6 inhibitor, on human
> liver microsomal cytochromes P450 (CYP) were studied
> to elucidate its selectivity....
>
> .... Potency and selectivity of tranylcypromine were
> strongly dependent on the amine group,"
>
> And even this (whatever it means!!!):
>
> "In human liver microsomes tranylcypromine induced type
> II and cyclopropylbenzene type I difference spectrum.
> According to the double reciprocal analysis of these
> spectral responses both tranylcypromine and cyclopropyl
> benzene may have at least two P450-related binding sites
> in liver microsomes."
>
> It seems better agreed that, as I posted before, Lamisil is a potent inhibitor of CYP2D6.
>
> Now what does all this mean? :-) Does it in any way help explain the fact that I had a strong "uplift" in the Parnate when I took Lamisil?
>
> .
Well, anything is possible, I suppose. I've come to the conclusion myself that Parnate is not as "irreversible" as Nardil is, based on references to this in the literature and my own personal experience with both drugs. However, most sources describe both drugs as being "irreversible," as if this is a black and white issue, when the reality is that it is somewhat more complicated than that.I have heard of possible interactions between Parnate (and Nardil) and the CYP-450 enzyme system but have not researched the topic to any real degree. However, being an inhibitor is not necessarily the same as being a substrate. Some drugs will inhibit a particular enzyme but are not actually metabolized by that enzyme; their own metabolism is dependent on some other enzyme or enzyme system. Regardless of whether it inhibits any of the CYP-450 enzymes, I do not believe Parnate is an actual substrate of any of them. As I indicated, it is instead a substrate (and inhibitor) of the MAO-A and MAO-B enzymes, which is why it has the particular antidepressant effects it has. If Lamisil is a CYP-450 2D6 inhibitor, that should, in itself, not matter even if Parnate is also a 2D6 inhibitor because Parnate is not actually metabolized by the CYP-450 2D6 enzyme; it is metabolized by MAO-A and MAO-B instead.
What I recall seeing in the PDR about the Lamisil is a reference to possible interactions between it and certain MAO-B inhibitors, but I have no comprehension of why this should be. I'm afraid my knowledge of pharmacology is rather limited and pretty much restricted to the area of psychotropic drugs.
Todd
This is the end of the thread.
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