The pharmacological basis of coronary and systemic vasodilator actions of diazepam (Valium)

Abel, Ronald M.; Reis, Robert L.; Staroscik, Rudolf N.

doi:10.1111/j.1476-5381.1970.tb12890.x

Cited by 32 publications

(11 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While weaker in amplitude and relatively transient in duration (~30 min), these effects are consistent with the CNS depressive action of heroin—a presumed cause of acute, overdose-induced health complications. This decreased metabolic activity coupled with the enhanced heat loss from skin surfaces makes the rat exceptionally susceptible to more dramatic decreases in brain and body temperatures if large-dose heroin use is combined with other drugs with CNS inhibiting and vasodilatory actions such as alcohol (Gillespie, 1967; Volkow et al, 1990) and benzodiazepines (Sari et al, 1975; Abel et al, 1970; Kiyatkin and Bae, 2008). …”

Section: Discussionmentioning

confidence: 99%

Brain temperature effects of intravenous heroin: State dependency, environmental modulation, and the effects of dose

Bola

Kiyatkin

2017

Neuropharmacology

View full text Add to dashboard Cite

Here we examined how intravenous heroin at a dose that maintains self-administration (0.1 mg/kg) affects brain temperature homeostasis in freely moving rats under conditions that seek to mimic some aspects of human drug use. When administered under standard laboratory conditions (quiet rest at 22°C ambient temperature), heroin induced moderate temperature increases (1.0–1.5°C) in the nucleus accumbens (NAc), a critical structure of the brain motivation-reinforcement circuit. By simultaneously recording temperatures in the temporal muscle and skin, we demonstrate that the hyperthermic effects of heroin results primarily from inhibition of heat loss due to strong and prolonged skin vasoconstriction. Heroin-induced brain temperature increases were enhanced during behavioral activation (i.e., social interaction) and in a moderately warm environment (29°C). By calculating the “net” effects of the drug in these two conditions, we found that this enhancement results from the summation of the hyperthermic effects of heroin with similar effects induced by either social interaction or a warmer environment. When the dose of heroin was increased (to 0.2, 0.4, 0.8, 1.6, 3.2, and 6.4 mg/kg), brain temperature showed a biphasic down-up response. The initial temperature decrease was dose-dependent and resulted from a transient inhibition of intra-brain heat production coupled with increased heat loss via skin surfaces—the effects typically induced by general anesthetics. These initial inhibitory effects induced by large-dose heroin injections could be related to profound CNS depression—the most serious health complications typical of heroin overdose in humans.

show abstract

Section: Discussionmentioning

confidence: 99%

Brain temperature effects of intravenous heroin: State dependency, environmental modulation, and the effects of dose

Bola

Kiyatkin

2017

Neuropharmacology

View full text Add to dashboard Cite

show abstract

“…It is noteworthy that diazepam exerts considerable coronary vasodilator activity (Abel, Reis, & Staroscik, 1970a;1970b;Daniell, 1975) which is greater in patients with ischaemic heart disease (Ikram, Rubin & Jewkes, 1973). Previous investigations intent on elucidating the mechanism underlying this coronary vasodilator activity of diazepam revealed that the mechanism was independent of systemic effects and required that diazepam be delivered to the coronary circulation (Abel et al, 1970).…”

Section: Discussionmentioning

confidence: 99%

Potentiation of the Effects of Adenosine on Isolated Cardiac and Smooth Muscle by Diazepam

Clanachan

Marshall

1980

British J Pharmacology

View full text Add to dashboard Cite

Adenosine (10−7 to 3 times 10−4 m) or 2‐chloroadenosine (10−8 to 10−5 m) produced concentration‐dependent inhibition of the responses of the rat isolated vas deferens to electrical field stimulation. In electrically driven (2 Hz) guinea‐pig isolated left atria, adenosine (10−6 to 10−3 m) or 2‐chloroadenosine (10−8 to 10−7 m) produced concentration‐dependent decreases in isometric tension. Diazepam (10−6 and 10−5 m) had no direct effect per se, but significantly potentiated the inhibitory action of adenosine on both tissues without altering the inhibitory effect of 2‐chloroadenosine. The adenosine uptake inhibitors, hydroxynitrobenzylthioguanosine (HNBTG, 10−5 m) and dipyridamole (10−5 m) also potentiated the inhibitory actions of adenosine in rat vas deferens, but not those of 2‐chloroadenosine. Following adenosine uptake inhibition in rat vas deferens by HNBTG (10−5 m), diazepam (10−5 m) failed to produce any significant further potentiation of the inhibitory action of adenosine. It is concluded that the potentiation of adenosine by diazepam is possibly due to an inhibition of adenosine uptake.

show abstract

“…PRINDLE et al [2], in 1970, however did not observe these depressant actions related to the use of diazepam in isolated papillary cat muscles. In the same year, ABEL et al [3], using a canine model, reported an improvement in the contractile force of the myocardium after the use of diazepam and credited this effect on an increase in the coronary blood flow, a fact that was later contested by DANIELL [4].…”

Section: Introductionmentioning

confidence: 99%

Análise comparativa dos efeitos do diazepam, midazolam, propofol e etomidato na contratilidade miocárdica e no fluxo coronariano: estudo em corações isolados de ratos

Medeiros¹,

Pontes²,

Gomes³

et al. 2004

Rev Bras Cir Cardiovasc

View full text Add to dashboard Cite

Objective: The effects on myocardial contractility (dT/dt max ) and coronary blood flow of common drugs used in clinical practice (diazepam, midazolam, propofol and etomidate) were studied.Method: Fifty Wistar rat hearts were divided into five groups of ten and perfused using the Langendorff method with Krebs-Henseleit solution (K-H), with the perfusion pressure stable at 90 cm H 2 O and the temperature at 37.0 ± 0.5 °C. With the exception of Group I (control), they were submitted to single one-minute infusions of diazepam (50 micrograms) -Group II; midazolam (25 micrograms) -Group III; propofol (25 and 50 micrograms) -Group IV and etomidate (25 micrograms) -Group V. The drugs were diluted in 0.1 mL of K-H solution and the coronary blood flow rate and perfusion pressure controlled during infusion. The heart rate (beats per minute), myocardial tension (grams) and coronary blood flow (millimeters per minute) were measured at 1, 3, 5, 10, 15, 20, 25 and 30 minutes. The myocardial contractility was obtained by calculating the first derived tension/time (dT/dt max ), at each time interval.Results: The heart rate showed variations in Groups I, III and IV. A variation in the myocardial tension was seen in all groups except Group I and alterations in the coronary blood flow were seen in all groups except Group IV during the experiment. The myocardial contractility decreased in all groups, except for Group I.Conclusion: The assayed drugs diminished the myocardial contractility (p<0.05); the variations of the coronary blood flow were not directly correlated to those that occurred with the myocardial contractility.Descriptors: Myocardial contraction. Diazepam. Midazolam. Propofol. Etomidate. Resumo: Objetivo: Avaliar o efeito, na contratilidade miocárdica e no fluxo coronariano, de drogas comumente utilizadas na prática clínica (diazepam, midazolam, propofol e etomidato).Método: Foram estudados 50 corações isolados de ratos Wistar divididos em cinco grupos de dez, em preparação de Langendorff com líquido de perfusão de Krebs-Henseleit (K-H), mantendo-se constantes a pressão de perfusão (90 centímetros de água) e a temperatura (37° + 0,5 graus Celsius). Com exceção do Grupo I (Controle), foram feitas infusões Análise comparativa dos efeitos do diazepam, midazolam, propofol e etomidato na contratilidade miocárdica e no fluxo coronariano: estudo em corações isolados de ratosEffects of diazepam, midazolam, propofol and etomidate in myocardial contractility and coronary blood flow: comparative analysis in isolated rat's hearts 158 MEDEIROS, CGS ET AL -Effects of diazepam, midazolam, propofol and etomidate in myocardial contractility and coronary blood flow: comparative analysis in isolated rat's hearts Bras Cir Cardiovasc 2004; 19(2): 157-164 Rev

show abstract

The pharmacological basis of coronary and systemic vasodilator actions of diazepam (Valium)

Cited by 32 publications

References 11 publications

Brain temperature effects of intravenous heroin: State dependency, environmental modulation, and the effects of dose

Brain temperature effects of intravenous heroin: State dependency, environmental modulation, and the effects of dose

Potentiation of the Effects of Adenosine on Isolated Cardiac and Smooth Muscle by Diazepam

Análise comparativa dos efeitos do diazepam, midazolam, propofol e etomidato na contratilidade miocárdica e no fluxo coronariano: estudo em corações isolados de ratos

Contact Info

Product

Resources

About