Psycho-Babble Medication | about biological treatments | Framed
This thread | Show all | Post follow-up | Start new thread | List of forums | Search | FAQ

Merital (Nomifensine)

Posted by Deneb on October 9, 2009, at 23:26:46

Hey Miss Susan,

Here is what I found about Merital

Nomifensine maleate (Merital) is a norepinephrine-dopamine reuptake inhibitor[1] test-marketed in the United States by Hoechst AG (now Sanofi-Aventis) that increases the amount of synaptic dopamine available to receptors by blocking dopamine's re-uptake transporter. This is a mechanism of action shared by some recreational drugs like cocaine (see DRI).

Merital was investigated for use as an antidepressant in the 1970s, and was found to be a useful antidepressant at doses of 50-225mg per day, both motivating and anxiolytic. There were relatively few adverse effects (mainly dry mouth, headache, nausea), the drug was not sedating, did not interact significantly with alcohol and lacked anticholinergic effects. No withdrawal symptoms were seen after 6 months treatment. The drug was however considered not suitable for agitated patients as it presumably made agitation worse.

Later studies in the 1980s concluded that there was potential for dependence and abuse of nomifensine, typically in patients with a history of stimulant addiction, or when the drug was used in very high doses (400-600mg per day). Nomifensine is now only rarely used as an antidepressant due to concerns about causing haemolytic anaemia, and problems with overstimulation and hyperthermia in overdose. It has been investigated for use in treating ADHD and animal models of Parkinson's disease with some success. However, it has not proved of benefit to human patients suffering from advanced Parkinsonism.[2][3][4]

Nomifensine was withdrawn from mainstream medical use for a variety of reasons, abuse potential being a concern, but also problems with kidney and liver toxicity and haemolytic anaemia were cited, and some deaths were linked to the use of this compound although the mechanism remains unclear. A likely cause of nomifensine toxicity is the anilino group, as compounds containing this chemical substructure are notorious for producing toxic metabolites.[5]

Nomifensine is now mainly used in scientific research, particularly in studies involving dopamine release in response to addiction. This is because typically different areas of the brain have different amounts of dopamine transporter, but when Nomifensine is administered, a sufficient basal dopamine level is reached to allow comparison of dopamine release from drugs of abuse in different areas of the brain without the results being skewed by re-uptake speed variation.

The dihydroxylated analog of nomifensine is an interested analog that is known to have been reported.[6] (see also)[7]
[edit] Hexahydro-1H-indeno[1,2-b]pyridines

Anybody that is interested in nomifensine will be interested in learning about the related compounds of the present section.[8][9][10]

* Ro 8-4650

[edit] References

".... Merital (nomifensine) showed great promise as a pleasantly stimulating dopaminergic that also potently inhibits the reuptake of noradrenaline and - to a much lesser extent - serotonin. Motivation is typically enhanced. The product was marketed by its manufacturers Hoechst with the slogan "vive la difference!" Merital was withdrawn worldwide by its manufacturer from licensed use in 1986 after the discovery of its rare side-effect of precipitating a serious blood-disorder. For retarded melancholics, however, it was typically a very effective and well-tolerated mood-brightener with minimal side-effects. It is also a potentially valuable non-opioid analgesic. The risk/reward ratio of its carefully-monitored use may have been misjudged

Noradrenergic and dopaminergic effects of nomifensine in healthy volunteers
Scheinin M, Lindberg R, Syvalahti E,
Hietala J, Pihlajamaki K, Scheinin H
Clin Pharmacol Ther 1987 Jan; 41(1):88-96


Intravenous doses (100 mg in 20 minutes) of the antidepressant drug nomifensine, administered to male volunteers, increased heart rate and blood pressure, elevated the plasma levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), and powerfully stimulated growth hormone release and inhibited the secretion of prolactin. Oral nomifensine, either as a single 100 mg dose or as a similar dose after 2 weeks' treatment with the drug (150 mg/day), caused none of the above effects. This was in line with the limited (less than 30%) oral bioavailability of the active, unconjugated form of the drug, estimated in the same subjects. MHPG in plasma was slightly but consistently reduced by the 2 weeks' treatment, suggesting reduced turnover of norepinephrine. The observed clinical effects of nomifensine are compatible with uptake inhibition and augmented release of norepinephrine and dopamine and possibly direct agonistic effects on dopamine receptors. Although nomifensine was withdrawn from the market because of immunologic complications, it serves as a model compound of a new pharmacologic class of antidepressants, devoid of many of the disturbing side effects of the tricyclic drugs.




Post a new follow-up

Your message only Include above post

Notify the administrators

They will then review this post with the posting guidelines in mind.

To contact them about something other than this post, please use this form instead.


Start a new thread

Google www
Search options and examples
[amazon] for

This thread | Show all | Post follow-up | Start new thread | FAQ
Psycho-Babble Medication | Framed

poster:Deneb thread:920343