Etybenzatropine (INN), also known asethybenztropine (USAN, BAN) andtropethydrylin, is a syntheticanticholinergic andantihistamine drug previously marketed under the trade namesPanolid,Ponalid, andPonalide for the treatment ofParkinson's disease andparkinsonism.[1] Structurally related tobenzatropine, etybenzatropine combines a tropane backbone with antihistaminic properties, acting primarily as a muscarinic acetylcholine receptor antagonist. It was used to alleviate motor symptoms such as tremor and rigidity but has been discontinued due to limited efficacy, significant side effects, and the availability of more effective antiparkinsonian therapies.[citation needed] Etybenzatropine may exhibit weakdopamine reuptake inhibitor activity, though this is not well-established.[2]
Etybenzatropine is a centrally acting anticholinergic that blocks muscarinic acetylcholine receptors, particularly M1 receptors, in the basal ganglia, reducing the cholinergic-dopaminergic imbalance in parkinsonism.[2] Its tropane structure, featuring a diphenylmethoxy group, enhances anticholinergic potency while conferring antihistaminic effects similar topyrilamine.[3] The antihistaminic activity contributes to sedation, a common side effect.[2] Claims of dopamine reuptake inhibition, potentially increasing striatal dopamine, lack robust evidence and are considered speculative.[2] Etybenzatropine’s oral bioavailability is low due to hepatic first-pass metabolism, with metabolites excreted in urine and bile.[3]
Etybenzatropine was used to manage motor symptoms of Parkinson’s disease, such as tremor and rigidity, and drug-induced parkinsonism from antipsychotics.[2] Administered orally at 6–30 mg/day, dosages were titrated to balance efficacy and side effects.[2] It was less effective for bradykinesia and did not address non-motor symptoms like cognitive impairment.[3] Marketed as Panolid, Ponalid, and Ponalide in the mid-20th century, its use has been superseded bylevodopa, dopamine agonists, and other anticholinergics.[2]
Etybenzatropine’s side effects include dry mouth, blurred vision, constipation, urinary retention, and sedation due to its anticholinergic and antihistaminic properties.[2] Sedation often precludes its use in patients requiring alertness, such as drivers.[2] Severe adverse effects, though rare, include hyperpyrexia, toxic psychosis, and coma, particularly when combined with other anticholinergics or antihistamines likephenothiazines.[2] Interactions withtricyclic antidepressants or neuroleptics can exacerbate anticholinergic toxicity, posing risks of hyperthermia and delirium, especially in the elderly.[3]
Developed in the mid-20th century, etybenzatropine emerged from efforts to create anticholinergics for parkinsonism, building on atropine derivatives.[2] Its design combined muscarinic antagonism with antihistaminic properties, inspired by drugs likediphenhydramine.[3] Marketed in the 1950s and 1960s, it was overshadowed by levodopa’s introduction in the late 1960s, which offered superior efficacy for Parkinson’s disease.[2] Etybenzatropine’s development reflects early attempts to modulate dopaminergic deficits indirectly via cholinergic pathways.[3]
^Pourcher E, Bonnet AM, Kefalos J, Dubois B, Agid Y (1989). "Effects of etybenzatropine and diazepam on levodopa-induced diphasic dyskinesias in Parkinson's disease".Movement Disorders.4 (3):195–201.doi:10.1002/mds.870040301.PMID2779590.S2CID1826853.
