Effects of two newly synthesized analogues of lidocaine on rat arterial blood pressure and heart rate

N. M. Al Rasheed, M. I. Al Sayed, H. H. Al Zuhair, A. R.M. Al Obaid, A. J. Fatani

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

Two new analogues of lidocaine were synthesized at the College of Pharmacy, King Saud University: compound I (Methyl-2-[2-(N,N-diethylamino) acetamido]-3-cyano-4,5-dimethylbenzoate) and compound II (Methyl-2-[2-(piperidino) acetamido]-3-cyano-4,5-dimethylbenzoate). Their influence on the arterial blood pressure and the heart rate of urethane-anaesthetized rats was studied and compared with the actions of lidocaine. Compounds I, II and lidocaine induced significant dose-dependent decreases in the arterial blood pressure and heart rate, which usually returned to basal values within 3-5 min. There were significant differences in the potency of the three compounds in producing their effects on blood pressure and heart rate (P < 0.0001, ANOVA). Compound II was 14 and 6 times more potent in reducing blood pressure and 8 and 2 times more capable of reducing the heart rate than lidocaine and compound I, respectively. The results of this study also indicated the ineffectiveness of antagonists of autonomic, histaminergic and 5-HT receptor, and various vasodilators in blocking the actions of the three compounds on blood pressure and heart rate. Pretreatment with CaCl2 significantly reduced the hypotension and bradycardia induced by the three compounds, suggesting the involvement of calcium channels, probably of the L type. Several possible mechanisms are postulated. In conclusion, the results direct attention to the capability of the two new compounds to decrease blood pressure and heart rate; affects that may have clinical potential.

Original languageEnglish
Pages (from-to)313-319
Number of pages7
JournalPharmacological Research
Volume43
Issue number4
DOIs
Publication statusPublished - 1 Jan 2001

Fingerprint

Lidocaine
Arterial Pressure
Heart Rate
Blood Pressure
Controlled Hypotension
L-Type Calcium Channels
Serotonin Receptors
Urethane
Bradycardia
Vasodilator Agents
Analysis of Variance

Keywords

  • Blood pressure
  • Ca channels
  • Heart rate
  • Lidocaine
  • Na channels

Cite this

Al Rasheed, N. M. ; Al Sayed, M. I. ; Al Zuhair, H. H. ; Al Obaid, A. R.M. ; Fatani, A. J. / Effects of two newly synthesized analogues of lidocaine on rat arterial blood pressure and heart rate. In: Pharmacological Research. 2001 ; Vol. 43, No. 4. pp. 313-319.
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Effects of two newly synthesized analogues of lidocaine on rat arterial blood pressure and heart rate. / Al Rasheed, N. M.; Al Sayed, M. I.; Al Zuhair, H. H.; Al Obaid, A. R.M.; Fatani, A. J.

In: Pharmacological Research, Vol. 43, No. 4, 01.01.2001, p. 313-319.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Effects of two newly synthesized analogues of lidocaine on rat arterial blood pressure and heart rate

AU - Al Rasheed, N. M.

AU - Al Sayed, M. I.

AU - Al Zuhair, H. H.

AU - Al Obaid, A. R.M.

AU - Fatani, A. J.

PY - 2001/1/1

Y1 - 2001/1/1

N2 - Two new analogues of lidocaine were synthesized at the College of Pharmacy, King Saud University: compound I (Methyl-2-[2-(N,N-diethylamino) acetamido]-3-cyano-4,5-dimethylbenzoate) and compound II (Methyl-2-[2-(piperidino) acetamido]-3-cyano-4,5-dimethylbenzoate). Their influence on the arterial blood pressure and the heart rate of urethane-anaesthetized rats was studied and compared with the actions of lidocaine. Compounds I, II and lidocaine induced significant dose-dependent decreases in the arterial blood pressure and heart rate, which usually returned to basal values within 3-5 min. There were significant differences in the potency of the three compounds in producing their effects on blood pressure and heart rate (P < 0.0001, ANOVA). Compound II was 14 and 6 times more potent in reducing blood pressure and 8 and 2 times more capable of reducing the heart rate than lidocaine and compound I, respectively. The results of this study also indicated the ineffectiveness of antagonists of autonomic, histaminergic and 5-HT receptor, and various vasodilators in blocking the actions of the three compounds on blood pressure and heart rate. Pretreatment with CaCl2 significantly reduced the hypotension and bradycardia induced by the three compounds, suggesting the involvement of calcium channels, probably of the L type. Several possible mechanisms are postulated. In conclusion, the results direct attention to the capability of the two new compounds to decrease blood pressure and heart rate; affects that may have clinical potential.

AB - Two new analogues of lidocaine were synthesized at the College of Pharmacy, King Saud University: compound I (Methyl-2-[2-(N,N-diethylamino) acetamido]-3-cyano-4,5-dimethylbenzoate) and compound II (Methyl-2-[2-(piperidino) acetamido]-3-cyano-4,5-dimethylbenzoate). Their influence on the arterial blood pressure and the heart rate of urethane-anaesthetized rats was studied and compared with the actions of lidocaine. Compounds I, II and lidocaine induced significant dose-dependent decreases in the arterial blood pressure and heart rate, which usually returned to basal values within 3-5 min. There were significant differences in the potency of the three compounds in producing their effects on blood pressure and heart rate (P < 0.0001, ANOVA). Compound II was 14 and 6 times more potent in reducing blood pressure and 8 and 2 times more capable of reducing the heart rate than lidocaine and compound I, respectively. The results of this study also indicated the ineffectiveness of antagonists of autonomic, histaminergic and 5-HT receptor, and various vasodilators in blocking the actions of the three compounds on blood pressure and heart rate. Pretreatment with CaCl2 significantly reduced the hypotension and bradycardia induced by the three compounds, suggesting the involvement of calcium channels, probably of the L type. Several possible mechanisms are postulated. In conclusion, the results direct attention to the capability of the two new compounds to decrease blood pressure and heart rate; affects that may have clinical potential.

KW - Blood pressure

KW - Ca channels

KW - Heart rate

KW - Lidocaine

KW - Na channels

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U2 - 10.1006/phrs.2000.0783

DO - 10.1006/phrs.2000.0783

M3 - Article

VL - 43

SP - 313

EP - 319

JO - Pharmacological Research

JF - Pharmacological Research

SN - 1043-6618

IS - 4

ER -