PMID- 31642371
OWN - NLM
STAT- MEDLINE
DCOM- 20210810
LR  - 20210810
IS  - 1557-9042 (Electronic)
IS  - 0897-7151 (Print)
IS  - 0897-7151 (Linking)
VI  - 37
IP  - 6
DP  - 2020 Mar 15
TI  - Chronic, Twice-Daily Dosing of an NK2 Receptor Agonist 
      [Lys(5),MeLeu(9),Nle(10)]-NKA(4-10), Produces Consistent Drug-Induced Micturition 
      and Defecation in Chronic Spinal Rats.
PG  - 868-876
LID - 10.1089/neu.2019.6676 [doi]
AB  - Acute administration of [Lys5,Me,Leu9,Nle10]-NKA(4-10) (LMN-NKA) produces 
      contractions of the detrusor and rectum with voiding in intact and acutely spinal 
      cord injured (SCI) rats. In the current study, the ability of LMN-NKA (10 mug/kg 
      or 100 mug/kg, subcutaneous [SC], twice a day [bid]) or vehicle to induce voiding 
      and defecation in chronic SCI rats was examined across 30 days. After the last 
      day of administration, voiding response rates and bladder pressure (BP) responses 
      to LMN-NKA (intravenous [IV] and SC) were evaluated under anesthesia. In 
      conscious rats, LMN-NKA (100 mug/kg) produced dose-dependent micturition within 
      5 min, with response rates >90%, and voiding efficiency >80% in males and >60% in 
      females, which remained stable across the 1-month test period. Similarly, LMN-NKA 
      administration rapidly induced defecation, which also remained stable. Under 
      anesthesia, LMN-NKA increased BP, voiding efficiency, and voiding response rates, 
      which reached 100% at 3 and 10 mug/kg IV in males and females, respectively. SC 
      administration produced 100% response rates in males (30 mug/kg) but only 71% in 
      females (100 mug/kg). Efficacy in rats chronically treated with LMN-NKA was 
      similar to naive and vehicle-treated rats, except for reduced voiding efficiency 
      in chronically dosed female rats (100 mug/kg). No differences in bladder weights 
      or collagen-to-smooth muscle ratios in histological sections were seen between 
      the groups. Thus neither tolerance, nor sensitization, to LMN-NKA-induced 
      micturition and defecation occurs with chronic administration in rats with 
      chronic SCI. Efficacy was higher in male than in female rats.
FAU - Marson, Lesley
AU  - Marson L
AD  - Dignify Therapeutics LLC, Research Triangle Park, North Carolina.
FAU - Piatt, Raymond Keast 2nd
AU  - Piatt RK 2nd
AD  - Dignify Therapeutics LLC, Research Triangle Park, North Carolina.
FAU - Katofiasc, Mary A
AU  - Katofiasc MA
AD  - Dignify Therapeutics LLC, Research Triangle Park, North Carolina.
FAU - Bobbitt, Carol
AU  - Bobbitt C
AD  - Dignify Therapeutics LLC, Research Triangle Park, North Carolina.
FAU - Thor, Karl B
AU  - Thor KB
AD  - Dignify Therapeutics LLC, Research Triangle Park, North Carolina.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20191113
PL  - United States
TA  - J Neurotrauma
JT  - Journal of neurotrauma
JID - 8811626
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Neurokinin-2)
SB  - IM
MH  - Animals
MH  - Defecation/*drug effects/physiology
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Male
MH  - Peptide Fragments/*administration & dosage
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Neurokinin-2/*agonists/metabolism
MH  - Spinal Cord Injuries/*drug therapy/metabolism/physiopathology
MH  - Thoracic Vertebrae/injuries
MH  - Urination/*drug effects/physiology
PMC - PMC7071061
OTO - NOTNLM
OT  - cystometry
OT  - defecation
OT  - neurokinin 2 agonist
OT  - spinal cord injury
OT  - voiding
COIS- No competing financial interest exist
EDAT- 2019/10/24 06:00
MHDA- 2021/08/11 06:00
PMCR- 2021/03/15
CRDT- 2019/10/24 06:00
PHST- 2019/10/24 06:00 [pubmed]
PHST- 2021/08/11 06:00 [medline]
PHST- 2019/10/24 06:00 [entrez]
PHST- 2021/03/15 00:00 [pmc-release]
AID - 10.1089/neu.2019.6676 [pii]
AID - 10.1089/neu.2019.6676 [doi]
PST - ppublish
SO  - J Neurotrauma. 2020 Mar 15;37(6):868-876. doi: 10.1089/neu.2019.6676. Epub 2019 
      Nov 13.