← hubDrugs

Phenmetrazine

Discover related
Class
Dose
Duration

3 sources

← All substances
🔗 MergedCompareTripSitPharmacologyDrugCentral

Collated from TripSit, Pharmacology, DrugCentral. Where sources differ (e.g. dosing), Compare shows them side by side.

Sections
StimulantHabit-formingTS

Also known as preludinTS

Stimulant drug that was previously used as an appetite suppresant, has been withdrawn from the market, due to concerns of abuse and addiction. Usually produces less nervousness, euphoria, and insomnia than drugs of the amphetamine family. Also as a study concluded, it is slightly more effective than dextroamphetamine as a weight loss agent.TS

Oral

Route dataTripSit

Dose
WeakerStronger
ThresholdLightCommonStrongHeavy
——25–50 mg——+
050 mg
LightCommonStrongHeavy
Duration
ShorterLonger
Onset15–30 minutes
Total4–8 hours
After-effects1–12 hours
OnsetCome-upPeakOffset

🧬 Receptor activityDC

TargetActionAffinitySource
Sodium-dependent dopamine transporter (SLC6A3)Inhibitor6.883 EC50DRUGCENTRAL
Sodium-dependent noradrenaline transporter (SLC6A2)Inhibitor7.298 EC50DRUGCENTRAL
Amine oxidase [flavin-containing] A (MAOA)——DRUGCENTRAL
‹ PrevPage 1 / 11–3 of 3Next ›

Mechanism of actionPH

Phenmetrazine is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron leading to an increase in the release of these monoamines into the extraneuronal space. Dopamine integrates incoming sensory stimuli, initiates and controls fine movement (nigro-neostriatal pathway), controls emotional behavior (midbrain mesolimbic-forebrain system) and controls hypothalamic-pituitary endocrine system (tubero-infundibular system). It is this latter effect on the tubero-infundibular systm that seems to lead to reduced food intake. Phenmetrazine also acts as a monoamine oxidase inhibitor.
As with other amphetamine derivatives, no primary effect on appetite has been demonstrated with phenmetrazine & it is probable that its anorexigenic effect is secondary to CNS stimulation. /Phenmetrazine hydrochloride/
THEY DECREASE APPETITE BY STIMULATING THE HYPOTHALAMUS TO RELEASE CATECHOLAMINES IN THE CNS. ... ANOREXIANT DRUGS (EXCEPT FENFLURAMINE) INCREASE PHYSICAL ACTIVITY, & ALL OF THESE AGENTS HAVE METABOLIC EFFECTS INVOLVING FAT (INHIBITING LIPOGENESIS, ENHANCING LIPOLYSIS) AND CARBOHYDRATE METABOLISM, BUT THESE PROBABLY ARE SECONDARY TO SUPPRESSION OF APPETITE. /ANOREXIANTS/
The mechanisms of reinforcement are still uncertain /for many drugs/. ... Amphetamine & phenmetrazine appear to release newly synthesized neurotransmitter selectively, & their effects can be blocked by inhibition of tyrosine hydroxylase ...

PharmacodynamicsPH

Phenmetrazine is a sympathomimetic drug used primarily as an appetite depressant. Its actions and mechanisms are similar to dextroamphetamine. Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. Phenmetrazine was originally sold under the tradename Preludin as an anorectic. It has since been removed from the market. It is by some considered to have a greater potential for addiction than the amphetamines, and has been abused in many countries, for example Sweden.

Pharmacokinetics

Half-lifePH

16 to 31 hours
Following oral admin of a single 75 mg dose as conventional tablets, phenmetrazine has a plasma half life of about 8 hr in healthy adults. /Phenmetrazine hydrochloride/

AbsorptionPH

Readily absorbed from the gastro-intestinal tract and buccal mucosa.
Phenmetrazine hydrochloride is readily absorbed from the gastrointestinal tract ... Avg peak concn were obtained about 2 hr after ingestion. /Phenmetrazine hydrochloride/
A single dose of a sustained release prepn (Preludin Endurets) containing phenmetrazine 75 mg yielded blood concn at 8 & 12 hr after ingestion comparable to those obtained with the same dose of phenmetrazine hydrochloride ...
... The drug is excreted in urine principally as metabolites. Although elimination via biliary excretion (about 6% of a dose over 5 days) has been observed in rats, it is unlikely that appreciable biliary excretion occurs in humans. ... About 19% of a dose is excreted unchanged in urine within 24 hr. /Phenmetrazine hydrochloride/
Little unchanged 5-methyl-6-phenylmorpholine was excreted in the urine of either rats or guinea pigs, while man excreted approx 1/5 of the dose unchanged & the tamarin monkey 2/5.

MetabolismPH

Primarily hepatic (via CYP3A and CYP2D6). Resistant to metabolism by monoamine oxidase. Metabolism involves deamination to para-hydroxyamphetamine and phenylacetone; this latter compound is subsequently oxidize to benzoic acid and excreted as glucuronide or glycine (hippuric acid) conjugate. Smaller amounts of amphetamine are converted to norephedrine by oxidation.
In humans, principal urinary metabolites of the drug are lactam derivative & a phenolic hydroxyphenmetrazine derivative & its glucuronide; the drug also is metabolized to a nitrone derivative. /Phenmetrazine hydrochloride/
IN MAN, THE 24 HR METABOLITES OF ORALLY ADMIN PHENMETRAZINE (0.35 MG/KG) WERE 22% FREE & CONJUGATED 3-METHYL-2-(4-HYDROXYPHENYL)MORPHOLINE, 19% FENMETRAMIDE, & 5% UNKNOWN METABOLITE, WITH 19% UNCHANGED PHENMETRAZINE.
Little unchanged 5-methyl-6-phenylmorpholine was excreted in the urine of either rats or guinea pigs, while man excreted approx 1/5 of the dose unchanged & the tamarin monkey 2/5. More detailed analysis of the urine permitted the identification of 4 major metabolites. The phenol /derivative/ & its glucuronide are important in all species except the guinea pig. In this animal 5-methyl-3-oxo-6-phenylmorpholine was the major urinary metabolite. The inability of the guinea pig to ring-hydroxylate amphetamine derivatives is well known. A product of N-oxidation, tentatively identified as phenmetrazine nitrone, was found in appreciable quantities in the urine of the guinea pig & tamarin monkey.
Primarily hepatic (via CYP3A and CYP2D6). Resistant to metabolism by monoamine oxidase. Metabolism involves deamination to para-hydroxyamphetamine and phenylacetone; this latter compound is subsequently oxidize to benzoic acid and excreted as glucuronide or glycine (hippuric acid) conjugate. Smaller amounts of amphetamine are converted to norephedrine by oxidation.
Half Life: 16 to 31 hours

Plan when to take Phenmetrazine — see where onset, peak and comedown land on the clock

Fact-sheets from PsychonautWiki. Harm-reduction reference only — not medical advice.