3 sources
Collated from TripSit, Pharmacology, DrugCentral. Where sources differ (e.g. dosing), Compare shows them side by side.
Also known as dimenhydrinate, gravolTS
A combination of diphenhydramine and a mild stimulant to counteract the drowsiness accompanied by typical medical use of diphenhydramine. Roughly half the potency of DPH. Small doses can relieve motion sickness, reduce body load from opioids or DXM. Becomes a deliriant in high doses, keeping the user awake and often causing dysphoric, realistic hallucinations.TS
Oral
Route dataTripSit
| Threshold | Light | Common | Strong | Heavy |
|---|---|---|---|---|
| — | 100–250 mg | — | — | —+ |
| Onset | 30–90 minutes |
|---|---|
| Total | 5–8 hours |
🧬 Receptor activityPHDC
| Target | Action | Affinity | Source | |
|---|---|---|---|---|
| Histamine H1 receptor | — | Ki 37 nM | CHEMBL | TargetHistamine H1 receptor Action— AffinityKi 37 nM SourceCHEMBL |
| Muscarinic acetylcholine receptor M4 | — | Ki 80 nM | CHEMBL | TargetMuscarinic acetylcholine receptor M4 Action— AffinityKi 80 nM SourceCHEMBL |
| Muscarinic acetylcholine receptor M3 | — | Ki 95 nM | CHEMBL | TargetMuscarinic acetylcholine receptor M3 Action— AffinityKi 95 nM SourceCHEMBL |
| Muscarinic acetylcholine receptor M1 | — | Ki 109 nM | CHEMBL | TargetMuscarinic acetylcholine receptor M1 Action— AffinityKi 109 nM SourceCHEMBL |
| Muscarinic acetylcholine receptor M2 | — | Ki 164 nM | CHEMBL | TargetMuscarinic acetylcholine receptor M2 Action— AffinityKi 164 nM SourceCHEMBL |
| 5-hydroxytryptamine receptor 2A | — | Ki 198 nM | CHEMBL | Target5-hydroxytryptamine receptor 2A Action— AffinityKi 198 nM SourceCHEMBL |
| Muscarinic acetylcholine receptor M5 | — | Ki 227 nM | CHEMBL | TargetMuscarinic acetylcholine receptor M5 Action— AffinityKi 227 nM SourceCHEMBL |
| 5-hydroxytryptamine receptor 2C | — | Ki 332 nM | CHEMBL | Target5-hydroxytryptamine receptor 2C Action— AffinityKi 332 nM SourceCHEMBL |
| Sigma non-opioid intracellular receptor 1 | — | Ki 487 nM | CHEMBL | TargetSigma non-opioid intracellular receptor 1 Action— AffinityKi 487 nM SourceCHEMBL |
| 5-hydroxytryptamine receptor 2B | — | Ki 1097 nM | CHEMBL | Target5-hydroxytryptamine receptor 2B Action— AffinityKi 1097 nM SourceCHEMBL |
| Alpha-1D adrenergic receptor | — | Ki 1423 nM | CHEMBL | TargetAlpha-1D adrenergic receptor Action— AffinityKi 1423 nM SourceCHEMBL |
| Alpha-2A adrenergic receptor | — | Ki 1617 nM | CHEMBL | TargetAlpha-2A adrenergic receptor Action— AffinityKi 1617 nM SourceCHEMBL |
| Sodium-dependent dopamine transporter | — | Ki 1784 nM | CHEMBL | TargetSodium-dependent dopamine transporter Action— AffinityKi 1784 nM SourceCHEMBL |
| Sodium-dependent noradrenaline transporter | — | Ki 2020 nM | CHEMBL | TargetSodium-dependent noradrenaline transporter Action— AffinityKi 2020 nM SourceCHEMBL |
| Alpha-2B adrenergic receptor | — | Ki 2491 nM | CHEMBL | TargetAlpha-2B adrenergic receptor Action— AffinityKi 2491 nM SourceCHEMBL |
| Unchecked | — | Ki 3251 nM | CHEMBL | TargetUnchecked Action— AffinityKi 3251 nM SourceCHEMBL |
| Histamine H1 receptor (HRH1) | Antagonist | 7.432 Ki | DRUGCENTRAL | TargetHistamine H1 receptor (HRH1) ActionAntagonist Affinity7.432 Ki SourceDRUGCENTRAL |
| 5-hydroxytryptamine receptor 2A (HTR2A) | — | 6.703 Ki | DRUGCENTRAL | Target5-hydroxytryptamine receptor 2A (HTR2A) Action— Affinity6.703 Ki SourceDRUGCENTRAL |
| 5-hydroxytryptamine receptor 2B (HTR2B) | — | 5.96 Ki | DRUGCENTRAL | Target5-hydroxytryptamine receptor 2B (HTR2B) Action— Affinity5.96 Ki SourceDRUGCENTRAL |
| 5-hydroxytryptamine receptor 2C (HTR2C) | — | 6.479 Ki | DRUGCENTRAL | Target5-hydroxytryptamine receptor 2C (HTR2C) Action— Affinity6.479 Ki SourceDRUGCENTRAL |
| Alpha-1D adrenergic receptor (ADRA1D) | — | 5.847 Ki | DRUGCENTRAL | TargetAlpha-1D adrenergic receptor (ADRA1D) Action— Affinity5.847 Ki SourceDRUGCENTRAL |
| Alpha-2A adrenergic receptor (ADRA2A) | — | 5.791 Ki | DRUGCENTRAL | TargetAlpha-2A adrenergic receptor (ADRA2A) Action— Affinity5.791 Ki SourceDRUGCENTRAL |
| Alpha-2B adrenergic receptor (ADRA2B) | — | 5.604 Ki | DRUGCENTRAL | TargetAlpha-2B adrenergic receptor (ADRA2B) Action— Affinity5.604 Ki SourceDRUGCENTRAL |
| Cytochrome P450 2D6 (CYP2D6) | — | 5.821 IC50 | DRUGCENTRAL | TargetCytochrome P450 2D6 (CYP2D6) Action— Affinity5.821 IC50 SourceDRUGCENTRAL |
| Muscarinic acetylcholine receptor M1 (CHRM1) | — | 6.963 Ki | DRUGCENTRAL | TargetMuscarinic acetylcholine receptor M1 (CHRM1) Action— Affinity6.963 Ki SourceDRUGCENTRAL |
| Muscarinic acetylcholine receptor M2 (CHRM2) | — | 6.785 Ki | DRUGCENTRAL | TargetMuscarinic acetylcholine receptor M2 (CHRM2) Action— Affinity6.785 Ki SourceDRUGCENTRAL |
| Muscarinic acetylcholine receptor M3 (CHRM3) | — | 7.022 Ki | DRUGCENTRAL | TargetMuscarinic acetylcholine receptor M3 (CHRM3) Action— Affinity7.022 Ki SourceDRUGCENTRAL |
| Muscarinic acetylcholine receptor M4 (CHRM4) | — | 7.097 Ki | DRUGCENTRAL | TargetMuscarinic acetylcholine receptor M4 (CHRM4) Action— Affinity7.097 Ki SourceDRUGCENTRAL |
| Muscarinic acetylcholine receptor M5 (CHRM5) | — | 6.644 Ki | DRUGCENTRAL | TargetMuscarinic acetylcholine receptor M5 (CHRM5) Action— Affinity6.644 Ki SourceDRUGCENTRAL |
| Sigma non-opioid intracellular receptor 1 (SIGMAR1) | — | 6.312 Ki | DRUGCENTRAL | TargetSigma non-opioid intracellular receptor 1 (SIGMAR1) Action— Affinity6.312 Ki SourceDRUGCENTRAL |
| Sodium-dependent dopamine transporter (SLC6A3) | — | 5.749 Ki | DRUGCENTRAL | TargetSodium-dependent dopamine transporter (SLC6A3) Action— Affinity5.749 Ki SourceDRUGCENTRAL |
| Sodium-dependent noradrenaline transporter (SLC6A2) | — | 5.695 Ki | DRUGCENTRAL | TargetSodium-dependent noradrenaline transporter (SLC6A2) Action— Affinity5.695 Ki SourceDRUGCENTRAL |
Mechanism of actionPH
Dimenhydrinate is a theoclate salt that separates into [diphenhydramine] and [8-chlorotheophylline]. While the exact mechanism of action is unknown, diphenhydramine is theorized to reduce disturbances to equilibrium through antimuscarinic effects or histamine H1 antagonism. 8-chlorotheophylline may produce excitation through blocking adenosine receptors, reducing the drowsiness produced by diphenhydramine.
IT IS ESSENTIAL TO NOTE THAT NEITHER H1...BLOCKERS INHIBIT HISTAMINE RELEASE. ...EFFECTS OF HISTAMINE ANTAGONISTS...FACILITATE RELEASE. BENEFICIAL EFFECTS OF HISTAMINE ANTAGONISTS ARE THUS CONFINED TO ANTAGONISM OF RESPONSES TO HISTAMINE THAT IS RELEASED. /ANTIHISTAMINES/
DRUGS USED TO BLOCK HISTAMINE RECEPTORS FALL INTO THAT LARGE GROUP OF PHARMACOLOGICAL ANTAGONISTS THAT APPEAR TO ACT BY OCCUPYING "RECEPTIVE SITES" ON EFFECTOR CELL, TO EXCLUSION OF AGONIST MOLECULES, WITHOUT THEMSELVES INITIATING RESPONSE. TYPICALLY...COMPETITIVE & REVERSIBLE. /ANTIHISTAMINES/
...ANTIHISTAMINES EFFECTIVE IN MOTION SICKNESS ACT BY VIRTUE OF CENTRAL ANTAGONISM OF ACH... ACT BY BLOCKING EXCITATORY LABYRINTHINE IMPULSES @ CHOLINERGIC SYNAPSES IN REGION OF VESTIBULAR NUCLEI. /ANTIHISTAMINES/
...MOTION SICKNESS. ...STIMULATION OF VESTIBULAR APPARATUS...& THAT VESTIBULAR CEREBELLAR MIDBRAIN "INTEGRATIVE VOMITING CENTER" & MEDULLARY CHEMORECEPTIVE TRIGGER ZONE ARE SOMEHOW INVOLVED. /ANTIHISTAMINES/
PharmacodynamicsPH
Dimenhydrinate is indicated for the prevention and treatment of nausea, vomiting, or vertigo of motion sickness. It has a short duration of action of 4-8 hours. Patients should be counselled regarding pronounced drowsiness, avoiding alcohol and other sedatives, and exercising caution when operating a motor vehicle or heavy machinery.
Pharmacokinetics
Half-lifePH
The plasma elimination half life of dimenhydrinate is 5-8 hours.
AbsorptionPH
A 50 mg oral film coated tablet reaches a Cmax of 72.6 ng/mL with a Tmax of 2.7 hours. A 100 mg suppository reaches a Cmax of 112.2 ng/mL with a Tmax of 5.3 hours.
Dimenhydrinate is predominantly eliminated in the urine. 1-3% of the dissociated diphenhydramine is eliminated in the urine unchanged, while 64% of diphenhydramine is eliminated in the urine as metabolites. The elimination of dimenhydrinate has not been fully studied.
The volume of distribution of dimenhydrinate is 3-4 L/kg.
DIMENHYDRINATE (ETHANOLAMINES): DURATION OF ACTION (HR) 4-6. /FROM TABLE/
H1 ANTAGONISTS ARE READILY ABSORBED FROM GI TRACT & PARENTERAL SITES OF ADMIN. FOLLOWING ORAL ADMIN, EFFECTS START WITHIN 15 TO 30 MIN, ARE FULLY DEVELOPED WITHIN 1 HR, & LAST ABOUT 3 TO 6 HR, ALTHOUGH SOME...ACT LONGER. /ANTIHISTAMINES/
MetabolismPH
Dimenhydrinate is a theoclate salt that separates into [diphenhydramine] and [8-chlorotheophylline]. diphenhydramine can either be N-glucuronidated by UGTs to diphenhydramine N-glucuronide or N-demethylated by CYP2D6, CYP1A2, CYP2C9, and CYP2C19 to N-desmethyldiphenhydramine. N-desmethyldiphenhydramine can be N-demethylated again by the same enzymes to N,N-didesmethyldiphenhydramine, which undergoes oxidative deamination to form diphenylmethoxyacetic acid.
EXTENSIVE STUDIES OF METABOLIC FATE OF ANTIHISTAMINES HAVE BEEN LIMITED TO A FEW COMPD. ... MAIN SITE OF METABOLIC TRANSFORMATION IS LIVER. /ANTIHISTAMINES/
Protein bindingPH
Dimenhydrinate is 70-85% protein bound in plasma.
Plan a dose of Dimenhydrinate
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External links
Fact-sheets from PsychonautWiki. Harm-reduction reference only — not medical advice.