Tricyclic antidepressants and calcium channel blockers: interactions at the (−)-desmethoxyverapamil binding site and the serotonin transporter

Rehavi, Moshe; Carmi, Ranit; Weizman, Abraham

doi:10.1016/0014-2999(88)90396-2

Cited by 29 publications

(8 citation statements)

References 31 publications

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“…The finding with VP is consistent with a previous report for rat platelets (Pietraszek and Buczo, 1987), synaptosomes (Brown et al, 1986) and human platelets (Rehavi et al, 1986). These authors stressed that the inhibition was Ca2+-independent and not linked to the Ca"-channel-blocking activity.…”

Section: Discussionsupporting

confidence: 93%

Effects of mood‐stabilizing drugs on the peripheral serotonin transporter

Marazziti

Rotondo

Lenzi

et al. 1992

Human Psychopharmacology

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We studied the effect of lithium (L), carbamazepine (CBZ), valproic acid (VA), verapamil (VP) and nifedipine (NF) on the specific binding of 3H-imipramine (3H-IMI) to platelet membranes, as compared with clomipramine (CLO). The results showed that VP, NF and CLO exerted a concentration-dependent inhibition on the IMI binding; CLO had the most potent inhibitory effect. No effect was observed with L. CBZ or VA. These results suggest that while VP and NF interact with the 5-HT transporter complex, L, CBZ and VA do not. Therefore, their effective (or suggested) mood-stabilizing effects are likely to be related to different mechanisms.

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Section: Discussionsupporting

confidence: 93%

Effects of mood‐stabilizing drugs on the peripheral serotonin transporter

Marazziti

Rotondo

Lenzi

et al. 1992

Human Psychopharmacology

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“…Other anticonvulsants used in migraine prophylaxis include lamotrigine, a blocker of voltage-gated sodium channels, leading to inhibition of neuronal release of glutamate, and gabapentin, which in addition to its modulating role on GABA and glutamate synthesis [Taylor, 1997] has been shown to block calcium channels in CNS neurons as well as in dorsal root ganglion sensory neurons [Cohen, 2005;Martin et al, 2002]. Calcium channel blockers acting as competitive inhibitors of serotonin uptake in brain and platelets [Rehavi et al, 1988] have been shown to provide beneficial prophylactic effects in some migraine sufferers [Silberstein, 2006]. Flunarizine is considered the most effective of the calcium channel blockers [Cohen, 2005].…”

Section: Migraine and Ion Channel Genesmentioning

confidence: 99%

Migraine genetics and prospects for pharmacotherapy

Colson

Fernandez

Griffiths

2007

Drug Development Research

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Migraine is a common complex neurological disorder with a well-known but poorly characterized genetic liability. The search for migraine susceptibility genes has been the focus of intense research. It is now believed that common migraine is not a single gene disorder, but attributable to several potentially interacting genetic variants. These variants may differ in each sufferer and interact with environmental factors to set the individual migraine threshold. This genetic liability may play an important role in the clinical heterogeneity seen in migraine and also in the variability of treatment response. This review will look at genetic loci implicated in migraine to date and consider their current or prospective role in migraine therapy. To elucidate the complex nature of migraine genetic liability, approaches that consider detailed endophenotypic profiles that encompass treatment response may provide much more relevant information than simple end diagnosis. Drug Dev Res 68: 282-293, 2007. r 2007 Wiley-Liss, Inc.

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“…Tricyclic antidepressants are known to inhibit calcium currents in heart myocytes (Isenberg and Tamargo, 1985;Delpón et al, 1991) and in neurons (Ogata et al, 1989;Choi et al, 1992). They also modulate binding of dihydropyridines and that of diltiazem and gallopamil to the calcium channel (Schaeffer et al, 1991;Rehavi et al, 1993), and calcium antagonists of the verapamil type were shown to affect binding of [ 3 H]imipramine (Rehavi et al, 1988). However, no attempt was made to specify the mechanism of the interaction between the antidepressant drugs and the L-type calcium channel.…”

mentioning

confidence: 99%

Inhibition of the Cardiac L-Type Calcium Channel Current by Antidepressant Drugs

Zahradnı́k

Minarovic²,

Zahradníková³

2007

J Pharmacol Exp Ther

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Antidepressants inhibit many membrane receptors and ionic channels, including the L-type calcium channel. Here, we investigated the inhibition of calcium current (I Ca ) by antidepressants in enzymatically isolated rat ventricular myocytes using whole-cell patch clamp. The molecular mechanism of inhibition was studied by comparing the voltage and state dependence of antidepressant inhibition of I Ca to the respective properties of calcium antagonists, and by studying the effect of (Ϯ)-1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-[trifluoromethyl]phenyl)-3-pyridine carboxylic acid methyl ester (Bay K8644) or diltiazem on the inhibitory potency of the antidepressants. All selected antidepressants inhibited calcium currents reversibly and concentration-dependently. At a stimulation frequency of 0.33 Hz, the antidepressants imipramine, clomipramine, desipramine, amitriptyline, maprotiline, citalopram, and dibenzepin blocked I Ca , with IC 50 values of 8.3, 11.6, 11.7, 23.2, 31.0, 64.5, and 364 M. The antidepressant drugs shifted steady-state inactivation curves of I Ca to negative voltages. The extent of the shift was similar to that induced by diltiazem or verapamil, but it was significantly smaller than that induced by felodipine. The usedependent component of the antidepressant-induced block was similar to that of diltiazem, and it was significantly more and less, respectively, than those of felodipine and verapamil. In the presence of Bay K8644, antidepressants were more effective in inhibiting I Ca . However, the inhibitory effect of antidepressants was also augmented by diltiazem, suggesting that these drugs do not compete with diltiazem for a single binding site. These data suggest that antidepressants exert their inhibitory action on cardiac L-type calcium channels by a specific interaction at a receptor site similar to, but distinct from, the benzothiazepine site.

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Tricyclic antidepressants and calcium channel blockers: interactions at the (−)-desmethoxyverapamil binding site and the serotonin transporter

Cited by 29 publications

References 31 publications

Effects of mood‐stabilizing drugs on the peripheral serotonin transporter

Effects of mood‐stabilizing drugs on the peripheral serotonin transporter

Migraine genetics and prospects for pharmacotherapy

Inhibition of the Cardiac L-Type Calcium Channel Current by Antidepressant Drugs

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