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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by PaulB on June 13, 2001, at 16:51:58
I have done a search and found a few postings concerning the smart-drugs Adrafinil and Modafinil and hope some advice can be offered on some queries I have about Adrafinil.I am trying to find out about the mechanism of action of Adrafinil. I am interested in Adrafinil but curioius about exactly how it works. I suspect that it is an agonist of the alpha-1 receptors and works in a smilar way to Buspirone 'mimicking' the activity of noradrenaline at these receptors but Im not sure. Modafinil may work differently I think but Im not sure about this either. Difficult drugs to get concrete info one so any links would be apprececiated.
The other thing which interested me was why Adrafinil can take days to months to start working. Why such a wide lapse in possible onset of effect. My guess was the v-short half-life of Adrafinil. For people not taking it more regularly it will take longer.
I have some other queries but Ill wait to see if theres help amongst Dr-Bobs members first?
Posted by SalArmy4me on June 14, 2001, at 8:51:07
In reply to Questions About Adrafinil?, posted by PaulB on June 13, 2001, at 16:51:58
Adrafinil is believed to serve as an alpha-1 adrenoceptor agonist. The improved learning seen with it may also result from enhancement of vigilance due to facilitation of noradrenergic transmission in the central nervous system. Adrafinil stimulates the noradrenergic post-synaptic receptors and thereby boost alertness, activity and energy. --That's all I could find.
Posted by Mitch on June 14, 2001, at 10:16:31
In reply to Re: Questions About Adrafinil? » PaulB, posted by SalArmy4me on June 14, 2001, at 8:51:07
> Adrafinil is believed to serve as an alpha-1 adrenoceptor agonist. The improved learning seen with it may also result from enhancement of vigilance due to facilitation of noradrenergic transmission in the central nervous system. Adrafinil stimulates the noradrenergic post-synaptic receptors and thereby boost alertness, activity and energy. --That's all I could find.
Sal,
1) Is this currently available in the US?
2) I have heard something about it being a new alternative drug for ADHD. Is this true, is it effective?
3) Given its pharmaco profile, I wonder if it would be a great augmentor for AD's like Remeron (to reverse drowsiness/dizziness), or atypical AP's that make people feel dizzy that respond well otherwise. (reverse orthostatic hypotension)
Thoughts??Mitch
Posted by PaulB on June 14, 2001, at 12:30:21
In reply to Re: Questions About Adrafinil? » SalArmy4me, posted by Mitch on June 14, 2001, at 10:16:31
> > Adrafinil is believed to serve as an alpha-1 adrenoceptor agonist. The improved learning seen with it may also result from enhancement of vigilance due to facilitation of noradrenergic transmission in the central nervous system. Adrafinil stimulates the noradrenergic post-synaptic receptors and thereby boost alertness, activity and energy. --That's all I could find.
>
> Sal,
>
> 1) Is this currently available in the US?
> 2) I have heard something about it being a new alternative drug for ADHD. Is this true, is it effective?
> 3) Given its pharmaco profile, I wonder if it would be a great augmentor for AD's like Remeron (to reverse drowsiness/dizziness), or atypical AP's that make people feel dizzy that respond well otherwise. (reverse orthostatic hypotension)
> Thoughts??
>
> MitchThanks for the information.
I am not aware of Adrafinil being used for ADHD. The Dopamine class of drugs are best studied for this disorder although Venlafaxine has been used with some success. I should think it would be well worth a trial though.
Given that Remeron enhances noradrenaline at the alpha-1 post-synaptic receptors I shouldnt think Adrafinil would help with Remeron histamine induced sedation. It was my impression that Remeron sedation decreased after the antidepressant started working.
Posted by Mitch on June 14, 2001, at 23:21:20
In reply to Re: Questions About Adrafinil?, posted by PaulB on June 14, 2001, at 12:30:21
> Given that Remeron enhances noradrenaline at the alpha-1 post-synaptic receptors I shouldnt think Adrafinil would help with Remeron histamine induced sedation. It was my impression that Remeron sedation decreased after the antidepressant started working.
I mentioned that because I have noted that Remeron (and atypical and conventional antipsychotics) have *antagonist* properties (which are secondary to their intended receptors) at alpha-1 noradrenergic receptors which *causes* orthostatic hypotension and dizziness (not necessarily drowsiness-H1 receptor activity). I was thinking that if the dizziness component and *possibly* reduced alertness due to the a1 blockade was reversed with an a1 *agonist*, then meds such as Remeron might be more *tolerable* and more *effective*. Allowing the Remeron to function primarily from the 5-HT2 and 5HT-3 antagonism and wouldn't require as large a dose of Remeron to *overcome* the antihistamine sedation.
Mitch
Posted by PaulB on June 15, 2001, at 12:32:57
In reply to Re: Questions About Adrafinil? » PaulB, posted by Mitch on June 14, 2001, at 23:21:20
> > Given that Remeron enhances noradrenaline at the alpha-1 post-synaptic receptors I shouldnt think Adrafinil would help with Remeron histamine induced sedation. It was my impression that Remeron sedation decreased after the antidepressant started working.
>
> I mentioned that because I have noted that Remeron (and atypical and conventional antipsychotics) have *antagonist* properties (which are secondary to their intended receptors) at alpha-1 noradrenergic receptors which *causes* orthostatic hypotension and dizziness (not necessarily drowsiness-H1 receptor activity). I was thinking that if the dizziness component and *possibly* reduced alertness due to the a1 blockade was reversed with an a1 *agonist*, then meds such as Remeron might be more *tolerable* and more *effective*. Allowing the Remeron to function primarily from the 5-HT2 and 5HT-3 antagonism and wouldn't require as large a dose of Remeron to *overcome* the antihistamine sedation.
>
>
> MitchI guess an alpha-1 agonist such as Adrafinil or Modafinil could help. I dont know. Ive heard of antagonists to block agonists but not agonists to block antagonists before. I guess you have to take into account the effaciousness of Remeron, the degree of sedation and whether or not such a combination could be helpful. I think the augmentor Pinodol has a similar action to Remeron, blocking the 5-HT autoreceptors stimulating the release of 5-HT and increasing 5-HT at the 5-HT1a receptors only.
From what I have heard Remeron is the most sedating of all antidepressants alongside Trazadone. It is a potent anti-histamine even at low doses. Thats its first effect.
Posted by Mitch on June 15, 2001, at 23:33:51
In reply to Re: Questions About Adrafinil?, posted by PaulB on June 15, 2001, at 12:32:57
> > > Given that Remeron enhances noradrenaline at the alpha-1 post-synaptic receptors I shouldnt think Adrafinil would help with Remeron histamine induced sedation. It was my impression that Remeron sedation decreased after the antidepressant started working.
> >
> > I mentioned that because I have noted that Remeron (and atypical and conventional antipsychotics) have *antagonist* properties (which are secondary to their intended receptors) at alpha-1 noradrenergic receptors which *causes* orthostatic hypotension and dizziness (not necessarily drowsiness-H1 receptor activity). I was thinking that if the dizziness component and *possibly* reduced alertness due to the a1 blockade was reversed with an a1 *agonist*, then meds such as Remeron might be more *tolerable* and more *effective*. Allowing the Remeron to function primarily from the 5-HT2 and 5HT-3 antagonism and wouldn't require as large a dose of Remeron to *overcome* the antihistamine sedation.
> >
> >
> > Mitch
>
> I guess an alpha-1 agonist such as Adrafinil or Modafinil could help. I dont know. Ive heard of antagonists to block agonists but not agonists to block antagonists before. I guess you have to take into account the effaciousness of Remeron, the degree of sedation and whether or not such a combination could be helpful. I think the augmentor Pinodol has a similar action to Remeron, blocking the 5-HT autoreceptors stimulating the release of 5-HT and increasing 5-HT at the 5-HT1a receptors only.
>
> From what I have heard Remeron is the most sedating of all antidepressants alongside Trazadone. It is a potent anti-histamine even at low doses. Thats its first effect.
>PaulB,
I *liked* the positive effects of taking Remeron and the lack of some negative ones. BUT the antihistamine and orthostatic hypotension (dizziness) was just too much to bear for me to take. I tried up to 30mg/bedtime. Yes, the higher doses helped reduce some drowsiness, but the *dizziness* worsened with increased dosage. It felt like my body was following me around a foot or two behind me all the time-it really sucked. And it didn't get better with three months administration either-also gaining 30 lbs didn't help. If they could somehow *redesign* this med and get RID of the antihistamine and orthostatic hypotensive effects it could be a really BIG winner.
Mitch
Posted by JohnL on June 16, 2001, at 5:12:14
In reply to Questions About Adrafinil?, posted by PaulB on June 13, 2001, at 16:51:58
Here's some info I found on the web about Adrafinil. I've tried both Adrafinil and Modafinil, and in my opinion Adrafinil is much much better. I don't know why it takes days to weeks to work though. I felt it work almost immediately, but it did take a good 3 to 4 weeks for it to really take hold. As far as I can tell it is supposedly an alpha-1 agonist. However, clinical studies on rats indicate it also has action at D2 dopamine receptors. I think that may be true, because it acted synergistically for me when combined with Amisulpride or Zyprexa, both of which also act on dopamine D2.
For me Adrafinil alone was not good enough. But combined with minimum doses of Prozac and Zyprexa it has turned out to be like magic for me. I couldn't live without it.
ADRAFINIL (Olmifon)
Rapidly restores vigilance and alertness in older people and the physically and mentally tired. Has a powerful
antidepressant action far superior to that of fluoxetine (Prozac) and clomipramine (Anafranil) and is without any serious
side effects. Adrafinil restores your powers of concentration, memory and intellectual function. When administered to
older people who have lost interest in life, adrafinil makes them want to take part in life again and they find that they
have renewed energy and vigor. Adrafinil may be correctly described as an anti-aging drug because it directly combats
degeneration in the part of the brain that allows you to take pleasure in life. Elderly people very often have disturbed
sleep patterns and take many naps during the day. Adrafinil restores a youthful sleep/wake cycle of full alertness in the
daytime and deep restorative sleep at night. After several weeks of treatment with Adrafinil daytime sleepiness
disappears, interest in intellectual activity is restored and depression lifts. It is very important to note that this improved
quality of alertness is NOT accompanied with mental excitation and insomnia as occurs with amphetamine or caffeine.
The correct dosage is 300 to 600 mg per day. The dosage can be adjusted according to response. Remember it takes
three weeks for all the effects of Adrafinil to become apparent. Do not use Adrafinil if you have any type of kidney or liver
problem or if you suffer from epilepsy.
ADRAFINIL: What is; (a.k.a. Olmifon) (Description & information below)
NOTE:not to be confused with "Anafranil (a.k.a. clomipramine)" the Antidepressant.Adrafinil provides alertness in most without the feeling often felt with stimulants that usually are prescribed for a person with
narcolepsy. Such as amphetamines etc. Also the possibility of tolerance is low with its continued use. There is however a
need for certain Liver function tests
on a regular basis with its continued use. Normally the same types of required testing as with the medication " cylert " which is
commonly prescribed in the USA. It is also used in certain parts europe as a "antidepressant". It is the combination of
Adrafinil's releasing stimulantive arousal effect(s), and its antidepressant effects that some doctors in europe recommend
Adrafinil over its newer form of Modafinil. There have been studies done in the United States "measuring depression in
individuals with sleep disorders",. In one study it was suggested that the
"rate of narcolepsy and depression is estimated to be between 30-52%".ADRAFINIL
Adrafinil: Alertness Without StimulationAdrafinil is the prototype of a new class of smart drug - the eugeroics (ie, "good arousal") - designed to promote vigilance
and alertness. Developed by the French pharmaceutical company Lafon Laboratories, adrafinil (brand name, Olmifon) has
been approved in many European countries for treating narcolepsy, a condition characterized by excessive daytime sleepiness
and other unusual symptoms.Non-narcoleptic users generally find that adrafinil gives them increased energy and reduces fatigue, while improving cognitive
function, mental focus, concentration, and memory. It has been reported that quiet people who take adrafinil become more
talkative, reserved people become more open, and passive people become more active.Of course, many stimulant drugs, ranging from caffeine to methamphetamine, are known to produce similar alerting/energizing
effects. Adrafinil has been described by some users as a "kinder, gentler" stimulant, because it provides these benefits but
usually with much less of the anxiety, agitation, insomnia, associated with conventional stimulants.Adrafinil's effects are more subtle than those of the stimulants you may be used to, building over a period of days to months.
They appear to be based on its ability to selectively stimulate 1-adrenergic receptors in the brain.2 These receptors normally
respond to norepinephrine (noradrenaline), a neurotransmitter linked to alertness, learning, and memory. This is in contrast to
conventional stimulants, which stimulate a broader spectrum of brain receptors, including those involving dopamine. Its more
focused activity profile may account for adrafinil's relative lack of adverse side effects.Dosing
The standard dose is 2 to 4 300-mg tablets per day for improving cognitive function, although some people may find lower
doses produce a desirable degree of improvement. Higher doses have been used to treat narcolepsy.ADRAFINIL (OLMIFON)
A unique substance which improves daytime alertness and vigilance
without altering the phases of sleep. Take 2 to 4 tablets per day. After
8 to 10 days of treatment feelings of fatigue disappear, after 15 days
there is a powerful effect on activity and after 1 to 3 months cognitive
effects are experienced. Intellectual function is improved particularly,
the ability to formulate new ideas and recall information. Avoid if you
suffer from epilepsy, kidney or liver impairment.
> ADRAFINIL
>
> Submitted to the BIAM: 2/18/98
> Final entry: 3/23/2000
> Status: Validated
>
> Identification of substance
> Pharmacological properties
> Mechanisms of action
> Researched effects
> Therapeutic indications
> Side effects
> Genetic toxicity
> Drug Dependence
> Precautions
> Routes of administration
> Dosage and administration
> Pharmacokinetics
> Bibliography
>
> Identification of substance:
>
> Chemical formula:
> 2-[(diphenylmethyl)sulfinyl]-N-hydroxyacetamide
>
> List of names:
>
> CAS: 63547-13-7
> DCIR: ADRAFINIL
> Memorandum: Experimental code 2755: CRL 40028
> Dci: Adrafinil
> DCIp class: 69
> DCIr class: 22
> rINN ADRAFINIL
>
> Chemical class:
>
> Acetohydroxyamic Acid
>
> Regulation: Class I
>
> 1. Psychostimulant (primary usage)
>
> Mechanisms of action:
>
> 1. Principal
> Stimulant, central nervous system alpha-1 adrenergic agonist. Causes release of
serotnin and dopamine at high doses.
>
>
> Researched effects:
>
> 1. Psychotonic (primary)
>
> Therapeutic indications:
>
> Cerebral Senescence (primary)
>
> 1) Treatment for the symptoms of age-related difficulties with vigillance and
depression. Double-blinded studies against placebo demonstrated an improvement in
mental state in elderly subjects.
>
> Side Effects:
>
> 1) Determined to be very rare: Skin eruptions, gastric distress, psychomotor
excitation, mental confusion, depression, mania (in manic-depressive patients),
increase in alkaline phosphatases (with prolonged treatment).
>
> Genetic toxicity:
>
> 1. Non-teratogenic in animals (studies done in rat and rabbit)
> 2. Information lacking in humans
>
> Dependance:
>
> 1. None.
>
> Contraindications:
>
> 1) Epilepsy
> 2) Severe hepatocellular deficiency
> 3) Cirrhosis (marked increase in biodisposal in cirrhotics)
> 4) Severe renal deficiency
> 5) Athletes (Prohibited substance, Journal Officiel, 3/7/2000)
>
> Routes of administration:
>
> 1 - Oral
>
> Dosage and administration:
>
> Usual dose for oral administration in adults:
> 600 to 1200 mg/day.
> In the case of renal or hepatic deficiencies, reduce the dosage to 300-600mg/day.
>
> Pharmacokinetics:
>
> 1. Half-life: 1 hour
> 2. Elimination: Renal
>
> Absorbtion:
> One hour after taking orally, plasma concentration is maximal.
>
> Distribution:
> Bound to plasma proteins: 80%
> Half-life
> 1 hour
> Metabolism
> 75% level of hepatic metabilism in the liver to an acid derivative, then glucoronic
acid conjugation.
> Elimination
> Renal, essentially in the form of a glucoronic acid conjugate
>
> Bibliography:
> -Prescrire 1991;11:68-69
>
> Patents
>
> Unique active constituent in the following current French patents:
>
> Olmifon, 300mg tablets.
> ..
Posted by PaulB on June 16, 2001, at 10:21:06
In reply to Re: Questions About Adrafinil? » PaulB, posted by Mitch on June 15, 2001, at 23:33:51
> > > > Given that Remeron enhances noradrenaline at the alpha-1 post-synaptic receptors I shouldnt think Adrafinil would help with Remeron histamine induced sedation. It was my impression that Remeron sedation decreased after the antidepressant started working.
> > >
> > > I mentioned that because I have noted that Remeron (and atypical and conventional antipsychotics) have *antagonist* properties (which are secondary to their intended receptors) at alpha-1 noradrenergic receptors which *causes* orthostatic hypotension and dizziness (not necessarily drowsiness-H1 receptor activity). I was thinking that if the dizziness component and *possibly* reduced alertness due to the a1 blockade was reversed with an a1 *agonist*, then meds such as Remeron might be more *tolerable* and more *effective*. Allowing the Remeron to function primarily from the 5-HT2 and 5HT-3 antagonism and wouldn't require as large a dose of Remeron to *overcome* the antihistamine sedation.
> > >
> > >
> > > Mitch
> >
> > I guess an alpha-1 agonist such as Adrafinil or Modafinil could help. I dont know. Ive heard of antagonists to block agonists but not agonists to block antagonists before. I guess you have to take into account the effaciousness of Remeron, the degree of sedation and whether or not such a combination could be helpful. I think the augmentor Pinodol has a similar action to Remeron, blocking the 5-HT autoreceptors stimulating the release of 5-HT and increasing 5-HT at the 5-HT1a receptors only.
> >
> > From what I have heard Remeron is the most sedating of all antidepressants alongside Trazadone. It is a potent anti-histamine even at low doses. Thats its first effect.
> >
>
> PaulB,
>
> I *liked* the positive effects of taking Remeron and the lack of some negative ones. BUT the antihistamine and orthostatic hypotension (dizziness) was just too much to bear for me to take. I tried up to 30mg/bedtime. Yes, the higher doses helped reduce some drowsiness, but the *dizziness* worsened with increased dosage. It felt like my body was following me around a foot or two behind me all the time-it really sucked. And it didn't get better with three months administration either-also gaining 30 lbs didn't help. If they could somehow *redesign* this med and get RID of the antihistamine and orthostatic hypotensive effects it could be a really BIG winner.
>
> MitchI think you might be right. It stand alone at the moment as a novel antidepressant. If you really want to find out about Remeron theres information at Organon's website, manufacturer of Remeron. They have put together slides with commentary-audio and text-from conferences held about the drug. The pharmacology of Remeron is discussed in detail. I recommend you check it out.
Posted by Michael K on June 16, 2001, at 14:38:25
In reply to Re: Questions About Adrafinil?, posted by PaulB on June 16, 2001, at 10:21:06
> > > > > Given that Remeron enhances noradrenaline at the alpha-1 post-synaptic receptors I shouldnt think Adrafinil would help with Remeron histamine induced sedation. It was my impression that Remeron sedation decreased after the antidepressant started working.
> > > >
> > > > I mentioned that because I have noted that Remeron (and atypical and conventional antipsychotics) have *antagonist* properties (which are secondary to their intended receptors) at alpha-1 noradrenergic receptors which *causes* orthostatic hypotension and dizziness (not necessarily drowsiness-H1 receptor activity). I was thinking that if the dizziness component and *possibly* reduced alertness due to the a1 blockade was reversed with an a1 *agonist*, then meds such as Remeron might be more *tolerable* and more *effective*. Allowing the Remeron to function primarily from the 5-HT2 and 5HT-3 antagonism and wouldn't require as large a dose of Remeron to *overcome* the antihistamine sedation.
> > > >
> > > >
> > > > Mitch
> > >
> > > I guess an alpha-1 agonist such as Adrafinil or Modafinil could help. I dont know. Ive heard of antagonists to block agonists but not agonists to block antagonists before. I guess you have to take into account the effaciousness of Remeron, the degree of sedation and whether or not such a combination could be helpful. I think the augmentor Pinodol has a similar action to Remeron, blocking the 5-HT autoreceptors stimulating the release of 5-HT and increasing 5-HT at the 5-HT1a receptors only.
> > >
> > > From what I have heard Remeron is the most sedating of all antidepressants alongside Trazadone. It is a potent anti-histamine even at low doses. Thats its first effect.
> > >
> >
> > PaulB,
> >
> > I *liked* the positive effects of taking Remeron and the lack of some negative ones. BUT the antihistamine and orthostatic hypotension (dizziness) was just too much to bear for me to take. I tried up to 30mg/bedtime. Yes, the higher doses helped reduce some drowsiness, but the *dizziness* worsened with increased dosage. It felt like my body was following me around a foot or two behind me all the time-it really sucked. And it didn't get better with three months administration either-also gaining 30 lbs didn't help. If they could somehow *redesign* this med and get RID of the antihistamine and orthostatic hypotensive effects it could be a really BIG winner.
> >
> > Mitch
>
> I think you might be right. It stand alone at the moment as a novel antidepressant. If you really want to find out about Remeron theres information at Organon's website, manufacturer of Remeron. They have put together slides with commentary-audio and text-from conferences held about the drug. The pharmacology of Remeron is discussed in detail. I recommend you check it out.Does anyone know whether Adrafinil can be combined with MAOI. I currently take 70 mg Parnate daily. I recently been augmenting that with 10-15 mg Ritalin with some success. I've been curious whether Adrafinil would be a better option than the Ritalin. I purchased some Adrafinil a couple of months ago, but decided I needed more information before I tried it.
MK
This is the end of the thread.
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