![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
BY Li, JW Nalwalk, LA Barker, P Cumming, ME Parsons and LB Hough
Department of Pharmacology and Neuroscience, Albany Medical College, New York, USA.
The antinociceptive and pharmacological properties of the H2 receptor antagonist cimetidine and a novel cimetidine analog, SKF92374, were characterized. On both the hot-plate and tail-flick nociceptive tests, cimetidine and SKF92374 induced complete, dose-related analgesic responses when injected into the lateral ventricle of rats. SKF92374 showed strong similarities to cimetidine in analgesic efficacy, slope of dose-response curves and chemical structure, suggesting that these compounds share a common analgesic mechanism. In contrast, histamine induced submaximal antinociceptive effects, and the H3 antagonist thioperamide, a known HA-releasing drug, had little or no analgesic effects. Compared with cimetidine, SKF92374 showed very weak activity (400-fold lower affinity) on H2 receptors in vitro (isolated guinea pig atrium) and in vivo (rat gastric secretion). In addition, SKF92374 (100 microM) had neither agonist nor antagonist action on guinea pig ileum H1 receptors. SKF92374 was also a weak competitive antagonist of N alpha-methylhistamine-induced inhibition of electrically induced contractions of the guinea pig ileum (Kd = 5.2 microM), an H3 receptor- mediated response. Autoradiographic binding assays in guinea pig brain confirmed a weak antagonism of H3 receptors by SKF92374. The compound (up to 10 microM) also had no effect on unpurified rat brain histamine N-methyltransferase activity. These results support the hypothesis that cimetidine induces analgesia by a novel brain mechanism unrelated to H1, H2 or H3 receptors.
This article has been cited by other articles:
|
|
 |
|
  L. B. Hough, J. W. Nalwalk, R. Stadel, H. Timmerman, R. Leurs, B. C. Paria, X. Wang, and S. K. Dey Inhibition of Improgan Antinociception by the Cannabinoid (CB)1 Antagonist N-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A): Lack of Obligatory Role for Endocannabinoids Acting at CB1 Receptors J. Pharmacol. Exp. Ther., October 1, 2002; 303(1): 314 - 322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. B. Hough Genomics Meets Histamine Receptors: New Subtypes, New Receptors Mol. Pharmacol., March 1, 2001; 59(3): 415 - 419. [Full Text]
|
|
|
|
|
|
Y. Zhu, D. Michalovich, H.-L. Wu, K. B. Tan, G. M. Dytko, I. J. Mannan, R. Boyce, J. Alston, L. A Tierney, X. Li, et al. Cloning, Expression, and Pharmacological Characterization of a Novel Human Histamine Receptor Mol. Pharmacol., March 1, 2001; 59(3): 434 - 441. [Abstract] [Full Text]
|
|
|
|
|
|
L. B. Hough, J. W. Nalwalk, B. Y. Li, R. Leurs, W.M.P.B. Menge, H. Timmerman, M. E. Carlile, C. Cioffi, and M. Wentland Novel Qualitative Structure-Activity Relationships for the Antinociceptive Actions of H2 Antagonists, H3 Antagonists and Derivatives J. Pharmacol. Exp. Ther., December 1, 1997; 283(3): 1534 - 1543. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
