Interactions between analgesics and calcium channel blockers

1. The findings, derived from different experimental models, examined in this review, provide evidence that the calcium channel blockers and related drugs possess analgesic effects. 2. The antinociceptive action that some analgesic drugs exhibit may be related to calcium channel blockade. 3. Evidence from a variety of biochemical and pharmacological experimental approaches, support the existence of an interelation between the calcium modulators and the opioid drugs. 4. This idea agrees with the novel neuropharmacological hypothesis that a common very high affinity binding site for multiple neurotransmitters could exist, as has been proposed by Pasternak and Wood (1986). 5. This hypothesis could be extended to the neuromodulators or other neuromediators

Cholinergic transmission in vas deferens

1. 1. Prazosin, haloperidol, propranolol or timolol had no effect on the electrically evoked muscular twitch. 2. 2. Atropine was able to antagonize competitively acetylcholine (pA2 = 9.29 ± 0.30). 3. 3. The muscular twitch of the Octodon degus vas deferens was only partially abolished by atropine (53.2 ± 0.72). 4. 4. The present results can be interpreted assuming that the Octodon degus vas deferens has one component muscarinic in its innervation. © 1983

Analgesic action of clonixin, nifedipine and morphine using the formalin test

1. The analgesic effect of C1X, nifedipine, metamizol, indoprofen and morphine in the pain induced by formalin injection (formalin test) was studied. 2. Attempts to demonstrate tolerance to C1X were unsuccessful. 3. In the analgesic test nifedipine and morphine are approximately 10 times more potent than C1X. 4. The present results suggest that the analgesic action of C1X is not mediated by μ1, δ or κ-opioid receptors and the anti-nociceptive effect of nifedipine may be associated with the blockade of the transmembrane inward movements of calcium

Effect of pentazocine on the evoked potentials recorded in the primary somesthetic cortical areas of guinea pigs

The influence of pentazocine on the evoked potentials registered in the primary somesthetic cortical area in guinea pigs under pentobarbital anesthesia was studied. The stimulation was applied in the contralateral lip and the evoked cortical responses from different zones on the cortex stereotaxically localized were registered. Pentazocine (5-10 mg/kg i.v.) induced a significant increase in the latency of the evoked potentials as compared with controls. Since morphine does not modify these potentials, the effect of pentazocine is interpreted as being a direct one on the primary pain pathway. © 1975

Vasorelaxant effect of the analgesic clonixin on rat aorta

1. 1. A novel vasorelaxant effect of clonixinate of l-lysine (Clx), analgesic and anti-inflammatory, was studied in rat aortic rings. 2. 2. Clx completely relaxed aortic rings contracted by KCl 70 mM and together with its analog flunixin exhibited lesser potency but equal efficacy than verapamil. In comparison, indomethacin, which is a more potent cyclo-oxygenase inhibitor relaxed only about 40% of the maximal contraction of aortic rings. 3. 3. Furthermore, Clx antagonized Ca2+ dependent aortic contraction and BAY K-8644 induced aortic contraction suggesting its calcium antagonist character. 4. 4. From these results it can be concluded that the hypotensive effect seen in rats in vivo after Clx i.v. injection arises because of vasodilatory effect of Clx and gives further support to the proposal that the pharmacological mechanism of action of Clx should be calcium antagonism. © 1995

Effects of CDP-Choline on acetylcholine-induced relaxation of the perfused carotid vascular beds of the rat

1. The effects of an infusion of cytidine-5′-diphosphocholine (CDP-choline) on the relaxation induced by exogenous acetylcholine (ACh) was studied in the isolated and perfuded external (ECB) and internal (ICB) carotid vascular beds of the rat. Changes in perfusion pressure were recorded during a dose-response curve to ACh and after a 30 min perfusion with CDP-choline (1 mg/min). 2. ACh induced a dose-dependent relaxation in both vascular beds, indicating the presence of muscarinic receptors. The affinity of the receptors for ACh in the ICB was significantly lower than in the ECB (ED50: 120 ± 21.4 ng and 69 ± 10.3 ng, respectively). 3. In the ICB the infusion of CDP-choline for 30 min significantly shifted the dose-response curve to ACh to the left, potentiating the relaxation. This effect was not seen in the ECB. 4. The infusion of hemicholinium (4 μM) for 30 min together with CDP-choline completely prevented the potentiation of exogenous ACh-induced relaxation in the ICB. 5. The resu

Experimental cardio-depressant effects of clonixin

1. The cardiovascular effects of CLX were studied. 2. CLX induced hypotension, bradycardia, negative chronotropism and negative inotropism. 3. Electrophysiological studies showed a decrease of sinus venosus discharge frequency. The action potential configuration was changed: the overshoot amplitude and (dV/dt)max were reduced and duration increased. 4. CLX at higher concentrations displaced the maximum diastolic potential and phase 4 slow diastolic depolarization was lengthened. 5. The above findings could be explained by a depressant action of CLX on the electrical activity of the pacemaker cells, possibly by a modification of the slow calcium currents