Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxybutynin (Ditropan) is widely utilized in treatment of incontinence due to neurogenic bladder dysfunction. We prepared its R and S enantiomers and evaluated their antimuscarinic, Ca++-channel antagonistic and spasmolytic effects in guinea pig detrusor strips and ileal longitudinal muscle. Ussing chambers were used to assess inhibition of carbachol-induced mucosal Cl-secretion in vitro. The enantiomers and the racemate were also tested in in vivo preparations for local anesthetic activity and for antimuscarinic activity in the slow filling cystometrogram. Stereoselective antimuscarinic effects [R)OXY:(R/S)OXY:(S)OXY) were evident for isolated ileal longitudinal (0.12:1.0:4.5) and bladder detrusor muscle (0.5:1.0:13) isolated ileal mucosa (0.2:1:8.9) and acetylcholine stimulated phosphoinositide turn-over in vitro (0.24:1.0:39). Stereoselectivity was also evident for the volume-induced contractions of the cystometrogram in vivo (0.7:1:15). In contrast, no stereoselectivity was observed for Ca++-channel antagonism, spasmolytic and local anesthetic properties of (R/S)OXY and its enantiomers.
 ...
PMID:R and S enantiomers of oxybutynin: pharmacological effects in guinea pig bladder and intestine. 284 72

(S)-Oxybutynin HCl (S-OXY) is a white crystalline solid powder with an acicular particle morphology. Differential scanning calorimetry (DSC) thermograms revealed one characteristic endotherm at 116.2 degrees C. On rescanning a sample heated to 120 degrees C, no thermal events were distinguished in the temperature range 25 degrees C to 150 degrees C. Weight loss curves determined by thermogravimetric analysis showed a continuous, gradual weight loss of about 0.15% over the temperature range 30 degrees C to 110 degrees C, followed by a change in slope and more rapid weight loss beginning at 150 degrees C. Observation by hot-stage microscopy confirmed the melting endotherm observed by DSC. Equilibrium moisture uptake studies indicated low water vapor uptake at low relative humidities (<52.8%). At relative humidities of 75.3% and 84.3%, S-OXY first deliquesced and then converted to a lower melting point crystal form. X-ray powder diffraction (XRPD) data supported the DSC findings. S-OXY underwent degradation by ester hydrolysis at alkaline pHs. The kinetics of this reaction were studied at 25 degrees C in carbonate-bicarbonate buffers. Observed rate constants of 0.008 h(-1) and 0.0552 h(-1) were determined at pH 9.69 and 10.25, respectively. The pKa of S-OXY was 7.75. The aqueous solubility of S-OXY was described as a function of pH and the free-base solubility. The mean partition coefficient log P was 3.33 using 1-octanol. The surface tensions of aqueous solutions of S-OXY decreased with increasing concentration, but no concentration-independent region was observed, indicating that S-OXY does notform micelles in aqueous solution. The dissolution rate of S-OXY from a compressed disk in 0.1 N HCl was rapid, whereas it was considerably slower at pH 7.4. Addition of 1% hexadecyltrimethylammonium bromide (CTAB) at pH 7.4 significantly improved the dissolution rate. S-OXY displayed very poor flow properties when compared to standard pharmaceutical excipients. XRPD results indicated that S-OXY exhibited a loss in crystallinity following ball milling. Hiestand tableting indices indicated that S-OXY has good bonding properties andforms strong compacts, but is likely to be susceptible to capping on ejection from the die. This indicated the needfor a plastically deformable excipient such as Avicel PH-101 in tablet formulations.
 ...
PMID:Preformulation studies on the S-isomer of oxybutynin hydrochloride, an Improved Chemical Entity (ICE). 1141 99