Overview on Reticuline and its metabolite(s), Salutaridine/Salutaridinol.

Reticuline is an alkaloid found in many poppies, the most well known is the Californian poppy, the flower of the State of California. Although, in this flower in particular which is used to treat Opioid dependency/addiction (source), showing that at least one alkane in this flower has a psychoactive property.

Reticuline has an LD50 of 251 mg/kg in mice, and 216 mg/kg in rats (source). In the same link, you can see that it also has the ability to impair motor-control and potentiate the effects of Phenobarbital, therefore proving that it has potent CNS depressant effects, very similarly to other opioids. In my opinion, confirming the previous statement and re-assuring the fact that it is in fact Reticuline creating the psychoactive properties of the Californian Poppy.

Reticuline is also known to block the Dopamine receptors (5HT1, 5HT3) (source)

Reticuline relies on a single enzyme to metabolise Salutaridine in the body, 4’-OMT is the name of this enzyme, and when in the presence of a different enzyme, SAM, it catalyses and is unable to be separated from SAM (source).

Reticuline can be synthesised into Salutaridine by a regioselective para-ortho oxidative coupling (source). In the body, Reticuline is metabolised by the cytochrome P-450 into Salutaridine, rendering it a opioid pro-drug.

Knowing that Reticuline has opioid properties, and directly metabolises into Salutaridine, we can now look at Salutaridine’s safety profile and dependance risk, and evaluate whether or not it is a medically sound drug.

Salutaridine, otherwise known as Floripavine, is a Morphinian μ-opioid receptor agonist (source) similar to Morphine, Fentanyl and Diacetylmorphine (Heroin) (list of μ-opioid agonists). Despite this, Salutaridine binds to the μ-opioid receptors with 10.000 fold less affinity than Morphine, but elicits half the protein-G activation (source) and has been proven to help with Oxycodone dependency (source).

Salutaridine is a commonly used precursor to Morphine and other Morphinian opioid-narcotic analgesics such as Codeine (.

Salutaridine is converted to Salutaridinol by the enzyme Salutaridine Reductase (SalR).

Excerpt taken from Wikipedia, confirming the previous statements and more information.

“In the morphine biosynthetic pathway, salutaridinol is derived in three steps from (R)-reticuline. First, (R)-reticuline undergoes an oxidation at each of its phenol rings mediated by the cytochrome P-450-dependent monooxygenase salutaridine synthase. These phenol group oxidations yield a diradical species that undergoes ortho coupling to the phenol group of the tetrahydroisoquinoline and para coupling to the benzyl group to create the salutaridinol precursor salutaridine. A stereospecific reduction of the salutaridine carbonyl group by salutaridine: NADPH 7-oxidoreductase then generates salutaridinol.”

Not a lot is known about Salutaridinol’s action directly (tests are usually done using Reticuline or Salutaridine).