{"doi":"10.3390/ijms22010020","title":"The Delta-Specific Opioid Glycopeptide BBI-11008: CNS Penetration and Behavioral Analysis in a Preclinical Model of Levodopa-Induced Dyskinesia","abstract":"In previous work we evaluated an opioid glycopeptide with mixed μ/δ-opioid receptor agonism that was a congener of leu-enkephalin, MMP-2200. The glycopeptide analogue showed penetration of the blood–brain barrier (BBB) after systemic administration to rats, as well as profound central effects in models of Parkinson’s disease (PD) and levodopa (L-DOPA)-induced dyskinesia (LID). In the present study, we tested the glycopeptide BBI-11008 with selective δ-opioid receptor agonism, an analogue of deltorphin, a peptide secreted from the skin of frogs (genus Phyllomedusa). We tested BBI-11008 for BBB-penetration after intraperitoneal (i.p.) injection and evaluated effects in LID rats. BBI-11008 (10 mg/kg) demonstrated good CNS-penetrance as shown by microdialysis and mass spectrometric analysis, with peak concentration levels of 150 pM in the striatum. While BBI-11008 at both 10 and 20 mg/kg produced no effect on levodopa-induced limb, axial and oral (LAO) abnormal involuntary movements (AIMs), it reduced the levodopa-induced locomotor AIMs by 50% after systemic injection. The N-methyl-D-aspartate receptor antagonist MK-801 reduced levodopa-induced LAO AIMs, but worsened PD symptoms in this model. Co-administration of MMP-2200 had been shown prior to block the MK-801-induced pro-Parkinsonian activity. Interestingly, BBI-11008 was not able to block the pro-Parkinsonian effect of MK-801 in the LID model, further indicating that a balance of mu- and delta-opioid agonism is required for this modulation. In summary, this study illustrates another example of meaningful BBB-penetration of a glycopeptide analogue of a peptide to achieve a central behavioral effect, providing additional evidence for the glycosylation technique as a method to harness therapeutic potential of peptides.","journal":"International Journal of Molecular Sciences","year":2020,"id":87875,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9457,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":446061,"name":"Omar S. Mabrouk","orcid":"0000-0001-5325-1944","position":1,"is_corresponding":false},{"id":446624,"name":"Lajos Szabó","orcid":null,"position":2,"is_corresponding":false},{"id":446062,"name":"Andrew J. Flores","orcid":"0000-0001-9472-2335","position":3,"is_corresponding":false},{"id":446625,"name":"Kate L. Parent","orcid":null,"position":4,"is_corresponding":false},{"id":385565,"name":"Jean M. Bidlack","orcid":"0000-0002-4305-5111","position":5,"is_corresponding":false},{"id":446063,"name":"Michael L. Heien","orcid":"0000-0001-5164-9596","position":6,"is_corresponding":false},{"id":307439,"name":"Robert T. Kennedy","orcid":"0000-0003-2447-7471","position":7,"is_corresponding":false},{"id":351847,"name":"Robin Polt","orcid":"0000-0003-0756-3183","position":8,"is_corresponding":false},{"id":446626,"name":"Scott J. Sherman","orcid":null,"position":9,"is_corresponding":false},{"id":446064,"name":"Torsten Falk","orcid":"0000-0003-4999-3309","position":10,"is_corresponding":false},{"id":446060,"name":"Mitchell J. Bartlett","orcid":"0000-0001-8280-5299","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T22:00:29.831859Z","pmid":"33374986","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}