Suppression of morphine and cocaine self-administration in rats by a mixed mu antagonist-kappa agonist (N-CBM-TAMO) and a long-acting selective D1 antagonist (AS-300)

1996 ◽  
Vol 6 (10) ◽  
pp. 1139-1144 ◽  
Author(s):  
Sydney Archer ◽  
Stanley D. Glick ◽  
Isabelle M. Maisonneuve ◽  
Jean M. Bidlack ◽  
Jimmy Y. Xu ◽  
...  
2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S996-S996 ◽  
Author(s):  
Annie Rein-Weston ◽  
Ismaiel Tekko ◽  
Lalit Vora ◽  
Courtney Jarrahian ◽  
Bill Spreen ◽  
...  

Abstract Background The purpose of this research was to develop a microarray patch (MAP; also known as a microneedle patch) for delivery of long-acting cabotegravir (CAB LA) for HIV pre-exposure prophylaxis (PrEP) and co-delivery of long-acting CAB LA and a hormonal contraceptive to enable a future multi-purpose prevention technology. This abstract presents preclinical pharmacokinetic results of MAP delivery of CAB LA. Methods MAPs are an alternative delivery technology in clinical development for intradermal delivery of vaccines and pharmaceuticals. A MAP consists of an array of micron-scale projections (<1 mm in height) amassed on a baseplate and applied to the skin like a bandage. MAPs could provide a discreet delivery system that enables self-administration, which could be particularly important for HIV prevention and contraception for young women and girls in low-resource settings. The purpose of this 3-year, USAID-funded project is to develop a MAP for delivery of long-acting HIV PrEP through to the point of Phase I clinical readiness. Key attributes of the MAP for long-acting HIV PrEP, as defined by our target product profile, include patch size similar to commercially available transdermal patches (20 to 140 cm2), wear-time of less than 24 hours (ideally 20 minutes), weekly or monthly administration to achieve therapeutic efficacy, and ideally successful self-administration after reading simple product instructions. Results We successfully formulated and optimized MAP projection geometry to accommodate high drug-loading requirements of CAB LA (5.86 mg CAB LA per 1 cm2 MAP), a hydrophobic drug. The MAPs are stable for 6 months under accelerated aging conditions in foil packaging, readily pierce the skin, and rapidly dissolve. In rats, plasma concentration levels of CAB LA were maintained above therapeutic targets of 4xPA-IC90 for 28 days; however, bioavailability was lower than IM or ID injection controls. Photos: QUB. MAPs dissolving over time in phosphate-buffered solution; MAP projections fully dissolved within 25 minutes. Conclusion Additional development work is warranted, including optimizing bioavailability, evaluating MAPs as a maintenance dose in vivo, conducting cost of manufacturing and cost of delivery analyses, and assessing potential end-user acceptability. Disclosures Bill Spreen, PharmD, ViiV Healthcare (Employee), Trevor Scott, RPh, PhD, ViiV Healthcare (Employee). Others Authors: No reported disclosures.


Medicina ◽  
2021 ◽  
Vol 57 (12) ◽  
pp. 1287
Author(s):  
Anna Sowa-Staszczak ◽  
Marta Opalińska ◽  
Anna Kurzyńska ◽  
Karolina Morawiec-Sławek ◽  
Aleksandra Gilis-Januszewska ◽  
...  

Background and Objectives: Long-acting somatostatin analogues (SSA) (octreotide LAR and lanreotide Autogel) are recommended as first line treatment of locally advanced or metastatic well-differentiated neuroendocrine tumors (NETs) with a good expression of somatostatin receptor (SSTR). Both of these SSAs are usually administered via injections repeated every 4 weeks. The purpose of the study was to compare the route of SSA administration (injection performed by professional medical staff and self-administration of the drug) with progression-free survival. Materials and methods: 88 patients in 2019 and 96 patients in 2020 with locally advanced or metastatic well-differentiated NETs were included in the study. All patients had a good expression of SSTR type 2 and had been treated for at least 3 months with a stable dose of long-acting somatostatin analogue every 4 weeks. All of them had received training on drug self-injections from professional NET nurses at the beginning of the COVID-19 epidemic. Results: The rate of NET progression in the study group in 2020 was higher than in 2019 29.1% vs. 18.1% (28 vs. 16 cases), p = 0.081. Conclusions: The method of administration of long-acting SSA injection performed by professional medical staff vs. self-injection of the drug may significantly affect the risk of NET progression. The unequivocal confirmation of such a relationship requires further observation.


Author(s):  
Marta Opalinska ◽  
Kurzynska Anna ◽  
Anna Sowa Staszczak ◽  
Palen-Tytko Joanna ◽  
Helena Zwinczewska ◽  
...  

2000 ◽  
Vol 152 (4) ◽  
pp. 414-421 ◽  
Author(s):  
Joshua A. Lile ◽  
Drake Morgan ◽  
Cory S. Freedland ◽  
Rachna S. Sinnott ◽  
Huw M.L. Davies ◽  
...  

2021 ◽  
Author(s):  
Joaquin E Douton ◽  
Nikhil K Acharya ◽  
Brooke Stoltzful ◽  
Dongxiao Sun ◽  
Patricia S. Grigson ◽  
...  

Substance use disorder is a difficult disease to treat due to its relapsing nature. In the last decade, opioid use disorder has been a threat to public health, being declared an epidemic by the Centers for Disease Control and Prevention. This is a tragic situation, considering there are currently effective, yet not ideal, treatments to prevent relapse. Recent research has shown that hormones that modulate hunger and satiety also can modulate motivated behavior for drugs of abuse. For example, the short-acting analog of glucagon-like peptide-1 (GLP-1), an incretin hormone that regulates homeostatic feeding, has been shown to reduce responding for rewarding stimuli such as food, cocaine, heroin and nicotine. Here, we tested the acute effects of the long-acting GLP-1 analog, liraglutide, on heroin seeking. We found that, in rats with heroin self-administration experience, subcutaneous (sc) administration of an acute dose of 0.3 mg/kg liraglutide was effective in preventing relapse after exposure to three major precipitators: drug-associated cues, stress, and the drug itself. However, the effects of the drug were contingent upon the pretreatment time, with the drug being fully effective when administered using a 6 h, rather than a 4 h pretreatment time. Finally, we confirmed that the reduction in drug seeking is not due to a locomotor impairment, as liraglutide did not significantly alter performance in a rotarod test. As such, this acute non-opioid treatment may serve as a new and effective bridge to treatment.


Life Sciences ◽  
1980 ◽  
Vol 27 (11) ◽  
pp. 971-978 ◽  
Author(s):  
Dietmar Römer ◽  
Heinz Büscher ◽  
Ronald C. Hill ◽  
Richard Maurer ◽  
Trevor J. Petcher ◽  
...  
Keyword(s):  

2019 ◽  
Vol 45 (4) ◽  
pp. 296-301 ◽  
Author(s):  
Rebecca Elizabeth Finch ◽  
Kevin McGeechan ◽  
Anne Johnstone ◽  
Sharon Cameron

IntroductionIn October 2017, Scotland legalised the home use of misoprostol for the purpose of early medical abortion (EMA). Women up to 9+6 weeks’ gestation can now self-administer the drug at home, 24–48 hours after receiving mifepristone in the clinic.ObjectiveTo evaluate the impact of this change on the uptake and success rate of EMA, and on the provision of effective contraception on discharge.MethodsA prospective observational study was conducted to compare the outcomes of two cohorts of women in the 6 months before and 6 months after the introduction of home administration of misoprostol. The main outcome measures were uptake of EMA, success of EMA and provision of long-acting reversible contraception (LARC) to women undergoing EMA.ResultsThere was a statistically significant increase in the uptake of EMA from 698/1075 (64.9%) women in the first study period to 823/1146 (71.8%) in the second study period. There was no statistically significant difference in the success rate of EMA: 99.3% and 98.9% in clinic and home misoprostol cohorts, respectively. There was also no statistically significant difference in the proportion of women provided with LARC: 37.7% and 33.7% in clinic and home misoprostol cohorts, respectively.ConclusionsSelf-administration of misoprostol at home increased uptake of EMA, with no effect on the high success rate that was previously seen with clinic administration of misoprostol. In addition, the reduced number of visits associated with home use of misoprostol has not affected the provision of effective contraception to women.


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