3 sources
🧬 Receptor activity
| 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 |
Mechanism of action
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/
Pharmacodynamics
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-life
The plasma elimination half life of dimenhydrinate is 5-8 hours.
Absorption
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/
Metabolism
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 binding
Dimenhydrinate is 70-85% protein bound in plasma.
External links
Fact-sheets from PsychonautWiki. Harm-reduction reference only — not medical advice.