Smooth muscle relaxing drugs and guinea pig ileum.

Mukai, Teiichi; Yamaguchi, Eiichi; Goto, Jun; Takagi, Keijiro

doi:10.1254/jjp.31.147

Cited by 22 publications

(11 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The relaxant effects of papaverine and theophylline may involve additional mechanisms. These drugs increase the efflux and uptake of Ca2" by intracellular organelles (Thorens & Haeusler, 1979;Takayanagi et al, 1980;Imai & Kitagawa, 1981;Koike & Takayanagi, 1981;Huddart et al, 1983;Qashi & Takayanagi, 1983) and also inhibit adenosine 3':5'-cyclic monophosphate (cyclic AMP) phosphodiesterase (Weiss & Hait, 1977;Mukai et al, 1981). Furthermore, recent evidence indicates that most of the calcium entry blockers have an additional intracellular site ofaction, related to an increase of Ca2" efflux or to stimulation of Ca2" uptake (Spedding, 1983;Saida & Van Breemen, 1983;Cohen et al, 1984).…”

Section: Discussionmentioning

confidence: 99%

Ketamine‐inhibition of calcium‐induced contractions in depolarized rat uterus: a comparison with other calcium antagonists

Calixto

Loch

1985

British J Pharmacology

View full text Add to dashboard Cite

1 The inhibitory effect of the intravenous anaesthetic ketamine on CaCl2-induced contractions in the isolated K+-depolarized uterus of the rat in Ca2+-free medium was compared with that produced by papaverine, theophylline and the calcium entry blocker verapamil.2 Pre-incubation for 20 min with either ketamine (0.3 to 3 mM), papaverine (3 to 30 IpM), theophylline (0.1 to mM) or verapamil (3 to 30 nM) induced parallel, concentration-dependent rightward displacements of the dose-response curves to Ca2+ (0.04 to 22 mM). The antagonism was competitive, except that due to verapamil, the Schild plot for which yielded a slope which differed significantly from unity. The calculated pA2 values (± s.e.mean) were: ketamine 3.90 ± 0.07; papaverine 5.55 ± 0.05; theophylline 3.99 ± 0.1 and verapamil 9.54 ± 0.24 3 These drugs differed in their ability to relax the sustained contraction induced by Ca2" (1 mM) in K+-depolarizing solution. Ketamine and verapamil relaxed the preparation in a concentrationdependent manner whereas theophylline and especially papaverine were less potent and induced only partial maximal relaxation. The tj of the relaxant effect was significantly less for ketamine than for verapamil (5 and 22 min, respectively). Only ketamine produced a relaxation comparable to that obtained by washing the preparation with Ca2+-free solution (t1 = approx. 5 min). 4 Prior exposure of the depolarized uterine strip to a low concentration of Ca2+ (0.22 mM) increased the potency of ketamine, but decreased that of papaverine and theophylline, in antagonizing Ca2+-induced contractions. In contrast, this procedure did not affect the potency of verapamil. 5 The inhibitory effects of these drugs, excluding those of verapamil, were completely reversed after washing the preparations with a high-potassium Ca2+-free solution, 3-5 times for about 30-60 min. 6 These experiments provide further evidence that the relaxant effect produced by ketamine on the rat isolated uterus is due to its ability to antagonize Ca2+ movements competitively and also show that there are marked differences between the nature of the relaxant effects of ketamine and those of papaverine, theophylline and verapamil.

show abstract

Section: Discussionmentioning

confidence: 99%

Ketamine‐inhibition of calcium‐induced contractions in depolarized rat uterus: a comparison with other calcium antagonists

Calixto

Loch

1985

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…papaverine, a benzylisoquinoline alkaloid, is a well known smooth muscle relaxing agent with multiple activities such as cyclic nucleotide phosphodiesterase (PDE) inhibitor and Ca 2ϩ channel blocker via specific binding to the benzothiazepine receptor site in the Ca 2ϩ channel. [2][3][4][5][6] Because of these multiple mechanisms it is useful as a non-specific spasmolytic agent but cannot be put to more specific use in cardiovascular and abdominal disorders. 7) However, if we take the chemical structure of papaverine as a model, we may find that small structural differences could lead to more useful compounds.…”

mentioning

confidence: 99%

Synthesis of N-Substituted Piperazinyl Carbamoyl and Acetyl Derivatives of Tetrahydropapaverine: Potent Antispasmodic Agents.

Kaur

Ghosh

Talwar

et al. 2002

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

The synthesis and structure-activity-relationship (SAR) for a series of N-substituted piperazinyl carbamoyl 7-15 and piperazinyl acetyl 18-26 derivatives of tetrahydropapaverine have been carried out. The general synthetic methods of carbamoyl tetrahydropapaverine analogues involve N-substituted piperazines and carbamoyl imidazole tetrahydropapaverine as starting materials. Another route for synthesizing these compounds, involving the formation of carbamoyl imidazole piperazine has also been explored. Acylation of tetrahydropapaverine followed by substitution with various piperazinyl moities afforded the acetyl tetrahydropapaverine derivatives. Variously substituted piperazines have been used to monitor the effect of electron releasing and electron withdrawing substituents upon the antispasmodic activity of the molecules. Effect of varying electron densities on the antispasmodic activity, by altering the position of these groups on the benzene ring has also been monitored. Pharmacological methods involve the in vitro antispasmodic activity studies on a freshly removed guinea pig ileum using a force displacement transducer amplifier connected to a physiograph. Among the analogues synthesized in the present study, a promising compound 7, a potent muscle relaxant as compared to papaverine has been obtained.

show abstract

“…It could be hypothesized that the effect observed may be related to the interaction of cholinergic system [28]. Indeed, a relationship between the cholinergic system and papaverine has been reported [28] indicating that papaverine caused a decrease both in the maximum height and the slope of dose-response curves induced by acetylcholine. Therefore, one might suggest that the effects observed may be related to an anticholinergic activity.…”

Section: Discussionmentioning

confidence: 98%

“…Considering that isoquinoline derivatives induce significant effects on guinea pig ileum by interacting with cholinergic, histaminergic as well as calcium system [14,27,28], the present paper reports the effect of isoquinoline alkaloids from A. mexicana and A. constricta as well as papaverine on contraction induced by naloxone in isolated guinea-pig ileum acutely exposed to morphine in vitro. Furthermore, the effect of isoquinoline alkaloids were also determined on DAMGO (highly selective mu-agonist) and U50-488H (highly selective kappa-agonist) withdrawal to test whether the possible interaction of these alkaloids on opioid withdrawal involves mu-and/or kappa-opioid receptors.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Isoquinoline Alkaloids on Opiate Withdrawal

Capasso

Piacente²,

Tommasi³

et al. 2006

CMC

View full text Add to dashboard Cite

Our interest has been centered on isoquinoline alkaloids obtained from Argemone mexicana (Papaveraceae), Aristolochia constricta (Aristolochiaceae) and the opium alkaloid, papaverine. In this respect, the effect of these isoquinoline alkaloids was investigated on contractions induced by naloxone of isolated guinea pig ileum acutely exposed to morphine in vitro. The activity of these alkaloids was compared to the control compound, papaverine. Furthermore, the effect of these isoquinoline alkaloids was also determined on naloxone-precipitated withdrawal in isolated guinea pig ileum exposed to DAMGO (highly selective mu opioid receptor agonist) and U50-488H (highly selective kappa opioid receptor agonist) to test whether the possible interaction of isoquinoline alkaloids on opioid withdrawal involves mu- and/or kappa-opioid receptors. Isoquinoline alkaloids from A. mexicana (from 5 x 10(-6) to 1 x 10(-4) M), from A. constricta (1 x 10(-5) x 10(-5)-1 x 10(-4) M) as well as papaverine treatment (1 x 10(-7)-5 x 10(-6)-1 x 10(-6) M) before or after the opioid agonists were able of both preventing and reversing the naloxone-induced contraction after exposure to mu (morphine and DAMGO) or kappa (U50-488H) opiate receptor agonists in a concentration-dependent manner. Both acetylcholine response and electrical stimulation were also reduced by isoquinoline alkaloids and papaverine treatment as well as the final opiate withdrawal was still reduced. The results of the present study indicate that isoquinoline alkaloids as well as papaverine were able to produce significant influence on the opiate withdrawal in vitro and these compounds were able to exert their effects both at mu and kappa opioid agonists.

show abstract

Smooth muscle relaxing drugs and guinea pig ileum.

Cited by 22 publications

References 26 publications

Ketamine‐inhibition of calcium‐induced contractions in depolarized rat uterus: a comparison with other calcium antagonists

Ketamine‐inhibition of calcium‐induced contractions in depolarized rat uterus: a comparison with other calcium antagonists

Synthesis of N-Substituted Piperazinyl Carbamoyl and Acetyl Derivatives of Tetrahydropapaverine: Potent Antispasmodic Agents.

The Effect of Isoquinoline Alkaloids on Opiate Withdrawal

Contact Info

Product

Resources

About