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H Schoemaker

Publications and source records attributed to H Schoemaker.

At least 19 recordsLinked to original sources
PubMed1992

Polyamines allosterically modulate [3H]nitrendipine binding to the voltage-sensitive calcium channel in rat brain.

The effects of polyamines on radioligand binding to the slow voltage-dependent Ca2+ channel were studied using membranes from the rat cerebral cortex. [3H]Diltiazem binding was inhibited by arcaine (IC50 = 55 microM) and, in decreasing order of potency, by agmatine, spermidine, spermine and putrescine. Under control conditions, only spermidine and spermine allosterically inhibited [3H]nitrendipine binding while arcaine, agmatine and putrescine were inactive. Nevertheless, putrescine antagonized the effect of spermine as well as the allosteric effects of diltiazem and verapamil on the binding of [3H]nitrendipine, in a manner analogous to that shown previously for Ca2+. Thus, polyamines may function as endogenous modulators of the voltage-dependent Ca2+ channel.

Allosteric Regulation↗
PubMed1992

Discriminative stimulus properties of 8-OH-DPAT: relationship to affinity for 5HT1A receptors.

Previous studies have shown that discriminative stimulus control established with the 5HT1A receptor agonist, 8-OH-DPAT, generalizes to other 5HT1A agonists and partial agonists but also to the alpha 2-adrenoceptor antagonist, yohimbine. On the basis of these results it has been proposed that the 8-OH-DPAT cue may be produced by activity at more than one receptor. In the present study rats were trained to discriminate a dose of 8-OH-DPAT (0.05 mg/kg, SC) from saline. Substitution tests showed dose-dependent generalisation with the 5HT1A compounds, buspirone, ipsapirone, MDL 72832 and MDL 73005EF, the alpha 2-adrenoceptor antagonists, yohimbine and idazoxan, and BMY 14802, which is usually described as a sigma ligand. The buspirone metabolite 1-pyrimidinyl piperazine (1-PP) which possesses mainly alpha 2-adrenoceptor antagonist properties produced only partial generalisation which was not dose related. Receptor binding studies showed that all the compounds which substituted for 8-OH-DPAT displaced [3H]-8-OH-DPAT binding to rat hippocampal membranes. Furthermore, there were statistically significant positive correlations between drug affinity for 5HT1A sites and their ED50 values for both substitution for 8-OH-DPAT and potency to decrease response rates. These results are consistent with the view that the 8-OH-DPAT cue, like the ability of the compounds tested to decrease rates of responding, is largely mediated by activity at 5HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

SL 84.0418: a novel, potent and selective alpha-2 adrenoceptor antagonist: in vitro pharmacological profile.

One novel, potent and selective alpha-2 adrenoceptor antagonist is 2-(4,5-dihydro-1H-imidazol-2-yl)-1,2,4,5-tetrahydro-2- propylpyrrolo[3,2,1-hi]-indole hydrochloride (SL 84.0418). It inhibits with high affinity the radioligand binding to rat cortical alpha-2 adrenoceptors, as well as to human platelet alpha-2 adrenoceptors labeled with [3H]idazoxan (Ki = 7 nM). SL 84.0418 has low affinity for alpha-1 adrenoceptors labeled with [3H]prazosin (Ki = 3.3 microM). In vitro, SL 84.0418 has no alpha agonist properties, whereas it is a potent alpha-2 adrenoceptor antagonist at both pre- and postsynaptic alpha-2 adrenoceptors. In contrast, it possesses low potency as an antagonist at postsynaptic alpha-1 adrenoceptors demonstrating a more than 1000-fold selectivity toward alpha-2 compared with alpha-1 adrenoceptors. In the same tests, the alpha-2 adrenoceptor antagonist idazoxan had a selectivity ratio of 200. SL 84.0418 is the racemic mixture of two enantiomers, SL 86.0715 [(+) enantiomer] and SL 86.0714 [(-) enantiomer]. The alpha-2 adrenoceptor blocking activities reside with SL 86.0715. Similar to idazoxan, SL 84.0418 increases in a concentration-dependent manner the electrically evoked release of [3H]norepinephrine from rat hypothalamic slices through the blockade of the presynaptic inhibitory alpha-2 adrenoceptors. In isolated hamster adipocytes, SL 84.0418 potently antagonizes the inhibition of lipolysis induced by UK 14,304. In addition, SL 84.0418 inhibits epinephrine-induced aggregation of rabbit platelets, effects mediated by postsynaptic alpha-2 adrenoceptors. SL 84.0418 does not inhibit (IC50 > 1,000 nM) radioligand binding to other receptors or recognition sites, nor does it inhibit calcium, sodium or potassium channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1991

Pharmacological characterisation and autoradiographic distribution of polyamine-sensitive [3H]ifenprodil binding sites in the rat brain.

Saturation studies with [3H]ifenprodil (in the presence of 3 microM (+)-3-PPP and 10 microM GBR 12909) demonstrated the presence of a high-affinity (Kd = 0.45 microM) population of binding sites in sagittal rat brain sections. This binding was inhibited by spermine (IC50 = 69 microM) and spermidine (IC50 = 623 microM) but not by putrescine (1 mM). Ifenprodil displaced this binding in a biphasic fashion with a high affinity component (IC50 = 0.992 microM) accounting for approximately 50% of the spermine-displaceable [3H]ifenprodil binding. The polyamine-sensitive [3H]ifenprodil binding sites were heterogenously distributed in the rat brain, the highest binding densities being found in the hippocampus and in the nucleus accumbens. The anatomical distribution of [3H]ifenprodil binding sites closely matches that previously reported for the N-methyl-D-aspartate (NMDA) receptor.

Animals↗
PubMed1991

Use of the clonal assay for the measurement of frequencies of HPRT mutants in T-lymphocytes from five control populations.

The clonal assay was used to measure frequencies of 6-thioguanine-resistant (HPRT) T-lymphocytes in 111 donors from the following 5 control populations: 55 adult healthy volunteers; 20 untreated cancer patients; 8 healthy hospital workers serving as controls for 9 hospital workers sterilizing equipment with ethylene oxide; 15 factory workers serving as controls for 15 workers occupationally exposed to high doses of ethylene oxide; 13 pretreatment samples from donors undergoing a diagnostic test with Technetium-99m for an analysis of heart function. With respect to mutant frequency (MF), cloning efficiency (CE) and age distribution, the first 4 populations were identical. The Technetium group had significantly higher MFs and lower CEs but this can be attributed to the higher mean age of this group. Using the total data base, we calculated the following relationships between MF, CE, age and smoking: (1) ln MF = 4.23-0.63 x ln CE indicating that a doubling of the CE has the effect of decreasing the MF by 37%, (2) ln MF = 0.71 + 0.03 x age meaning that the MF increases by 3% from one year to the next, (3) ln CE = 4.87-0.04 X age indicating that the CE decreases by 0.98% from one year to the next, (4) ln MF = 3.25-0.52 x ln CE + 0.02 X age being the equation quantifying the interrelationship between MF, CE and age, (5) ln MF = 3.32-0.56 x ln CE + 0.01 x age + 0.31 s (where s = 1 for smokers and s = 0 for nonsmokers). Using the latter equation, which allows for effects of CE and age on the MF, a statistically significant effect of smoking could be established. For any combination of CE and age smoking has the effect of increasing the MF by 36%. The above conclusions and calculations remain essentially the same when donors with cloning efficiencies lower than 10 or 20% are excluded from the data base.

Adolescent↗
PubMed1990

Luteinizing hormone and follicle stimulating hormone secretion patterns in girls throughout puberty measured using highly sensitive immunoradiometric assays.

Pulsatile gonadotrophin secretion patterns were studied in 36 healthy girls by measuring every 10 min and applying immunoradiometric assays (IRMA). Different stages of puberty were associated with significant changes in the plasma LH and FSH levels, pulse numbers (Pno) and pulse amplitudes (pA). Plasma LH was not detectable by day or night in young prepubertal girls (B1), neither was plasma oestradiol (E2); however, plasma FSH was detectable in a pulsatile pattern. In the older prepubertal girls (B1-onset) a discrete pulsatile LH pattern became detectable only during the night; plasma FSH tended to rise, while E2 became just detectable. In the early pubertal girls (B2) most daytime LH values were above the detection limit, in some with low-amplitude pulses. At night, pulses with a wide range of pulse amplitudes were detected. Plasma FSH increased further, plasma E2 only slightly. With the progression of puberty the plasma LH and FSH levels, Pno and pA increased significantly from stage B2 to B3 during the day (P less than or equal to 0.05) and close to significance during the night (0.05 less than or equal to P less than or equal to 0.1). However, in stage B4 the secretory characteristics tended to decline, while from stage B3 onwards plasma E2 started to rise rapidly (P less than or equal to 0.05, during the night from stage B2 to B3, during the day from B3 to B4m-). Simultaneous LH and FSH pulses were observed throughout puberty, usually during the night. Using these IRMA methods nocturnal LH in older prepubertal girls and both diurnal and nocturnal FSH pulsatility could be demonstrated in young prepubertal girls. From this study we conclude that (1) puberty in girls, as in boys, may be brought about by an increasing GnRH secretion both in frequency and amplitude, first appearing during the night. This increased GnRH stimulation results in LH secretion only during the night; (2) a cyclical pulsatile LH pattern including an LH surge can be established before the menarche; the capacity for positive feedback activity is not the final maturation characteristic to achieve an ovulatory menstrual cycle.

Adolescent↗
PubMed1989

Differences in the temperature dependence of drug interaction with the noradrenaline and serotonin transporters.

High affinity, sodium-dependent binding of [3H]mazindol is associated with the noradrenergic transporter while the binding of [3H]imipramine and [3H]paroxetine are associated with the serotonin transporter, e.g. in human platelets. In general radioligand binding studies to the monoamine transporters are performed at a temperature different from the physiological temperature (37 degrees C) at which uptake occurs. Previously reported data show a temperature dependence for tricyclic but not for nontricyclic inhibitors of the uptake of serotonin in their interaction with radioligand binding to the serotonin transporter. In the present study, both tricyclic and nontricyclic inhibitors of the uptake of noradrenaline were shown to have equal affinity for the binding of [3H]mazindol to the noradrenergic transporter at 0 degrees and 25 degrees C. Moreover, whereas serotonin transporter substrates inhibit the binding of [3H]imipramine/paroxetine in human platelets in an essentially temperature-independent manner (0-37 degrees C), noradrenaline transporter substrates are of higher affinity in inhibiting the binding of [3H]mazindol at 0 degrees C than at 25 degrees C. At 0 degrees C, substrate affinity for inhibition of the binding of [3H]mazindol to the noradrenaline transporter in the salivary gland of the rat approximates to the substrate affinity for transport by the noradrenaline carrier. The present data point to significant differences in the interaction of both substrates and inhibitors with the noradrenergic and serotonergic transporters, as studied using the radioligand binding. Thus, the pharmacological profile of the serotonin transporter, in terms of substrate and inhibitor affinity, is best studied using radioligand binding at 37 degrees C, whereas radioligand binding to the noradrenaline transporter is most representative at 0 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Luteinizing hormone and follicle stimulating hormone secretion patterns in boys throughout puberty measured using highly sensitive immunoradiometric assays.

Pulsatile gonadotrophin secretion patterns were studied in 32 normal boys (chronological age, CA 7.2-14.6 years) at different stages of pubertal development (5 in stage G1, 11 in G2, 5 in G3, 4 in G4, 7 in G5). Plasma LH and FSH concentrations were measured at 10 min intervals from 1200 to 1800 h and from 2400 to 0600 h using an immunoradiometric assay with a lower limit of detection of 0.15 IU/l for both LH and FSH. Plasma testosterone (T) was measured hourly. In the young prepubertal boys plasma LH was not detectable during day or night. In contrast, plasma FSH ranged from 0.7 to 1.4 IU/l. Plasma T was not detectable either (less than 0.25 nmol/l). In the older prepubertal boys a discrete pulsatile LH pattern (2 per 6 h) became discernible only during the night (range 0.1-0.4 IU/l). Plasma FSH also revealed a pulsatile pattern only during the night (2 per 6 h), while plasma T still remained undetectable. In the early pubertal boys (G2) a median daytime LH value of 0.37 IU/l was determined with 1 pulse per 6 h and at night definite LH pulses (4 per 6 h) were found in all boys (range 0.4-4.7 IU/l). Plasma FSH increased considerably to a median level of 2.50 IU/l during the day; most boys had a pulsatile FSH pattern (one per 6 h). Plasma T became detectable during the day (median 0.54 nmol/l) and night (median 1.16 nmol/l). With the progression of puberty the mean plasma level of LH and FSH, the LH/FSH pulse number and the LH/FSH pulse amplitude increased; plasma T rose as well, more obviously during the night. In G5, however, the LH pulse number decreased, while the LH level and pulse amplitude still increased, presumably as a result of the increased negative feedback action of sex steroids. Simultaneous LH/FSH pulses developed during the night at onset of puberty but during the day only towards the end of pubertal development. The use of these novel highly sensitive IRMA methods demonstrated nocturnal LH and both diurnal and nocturnal FSH pulsatility to be present in older prepubertal boys. The early detectable FSH level plus the existence of solitary FSH pulses throughout puberty as well as in adult men support the hypothesis of the existence of a GnRH-independent FSH secretion in men. Our results are in accordance with the following hypotheses: (1) puberty is brought about by GnRH secretion increasing with time, both in frequency and amplitude, and first appearing during the night.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Alpha-adrenoceptor subtypes in blood vessels: physiology and pharmacology.

The existence of alpha 1- and alpha 2-adrenoceptors subtypes is now well established. Presynaptically, alpha 2-adrenergic autoreceptors modulate norepinephrine release. In vascular smooth muscle both alpha 1- and alpha 2-adrenoceptors exist postjunctionally, the alpha 1 subtype being innervated preferentially in most vascular beds. alpha 2-Adrenoceptors may be present on the smooth muscle cell as well as the endothelial cell where they may participate in the release of endothelium derived relaxing and constricting factors. Developing insights into the role of alpha-adrenoceptor subtypes in the cardiovascular system, and into the classification of subtypes of alpha 1- and alpha 2-adrenoceptors may be expected to have, if confirmed, significant therapeutic implications for drug discovery in the cardiovascular system.

Animals↗
PubMed1989

Effects of Ca++ on [3H]diltiazem binding and its allosteric interaction with dihydropyridine calcium channel binding sites in the rat cortex.

In membranes from the rat cerebral cortex, the benzothiazepine [3H]diltiazem and the dihydropyridine [3H]nitrendipine label distinct but allosterically interacting calcium channel antagonist recognition sites. In the present study we evaluated the relationship between Ca++ and calcium channel antagonists binding sites within the voltage-dependent Ca++ channel. [3H]Nitrendipine binding to the rat cerebral cortex at 37 degrees C is not inhibited by Ca++, studied as CaCl2, in concentrations up to 10 mM. In contrast, [3H]diltiazem binding under these conditions is inhibited by Ca++ with an IC50 of 0.31 mM. The inhibition of diltiazem binding by Ca++ is reflected in an increase in the EC50 of diltiazem for enhancement of [3H]nitrendipine binding at 37 degrees C but not in the magnitude of its maximal heterotropic positive cooperative effect. Similarly, Ca++ increases the IC50 of verapamil for inhibition of [3H]nitrendipine binding at 37 degrees C without affecting the magnitude of its heterotropic negative cooperative effect. Schild analyses of these data indicate that Ca++ is an essentially competitive antagonist of the allosteric effects of diltiazem (KB = 0.32 mM) and verapamil (KB = 0.33 mM). At 0 degrees C, Ca++ is a negative allosteric inhibitor of the [3H]nitrendipine binding site (IC50 = 0.1 mM) and selectively increases the IC50 of diltiazem and verapamil for the inhibition of [3H]nitrendipine binding to membranes from the rat cerebral cortex. It may thus be suggested that the diltiazem and verapamil recognition sites are closely linked or identical with Ca++ binding site within the slow voltage-dependent Ca++ channel.

Allosteric Regulation↗
PubMed1988

Short-term lithium administration to healthy volunteers produces long-lasting pronounced changes in platelet serotonin uptake but not imipramine binding.

Platelet [3H]-5HT uptake, [3H]-imipramine binding and endogenous 5HT levels were measured in healthy volunteers during short-term (20 days) administration of lithium, and following its withdrawal. The Vmax of [3H]-5HT uptake was significantly decreased during lithium treatment. Following lithium withdrawal, platelet [3H]-5HT uptake (Vmax) remained decreased and was followed by a pronounced rebound effect in some of the subjects for up to 3 months. The affinity constant (Km) of [3H]-5HT uptake was not modified. Binding of tritiated imipramine during the same period and platelet 5HT levels measured till 14 days after withdrawal was not affected by lithium treatment. As lithium is devoid of in vitro effects on both 5HT uptake and imipramine binding, it is concluded that the effects of lithium on the 5HT transporter do not reflect a direct effect on the transporter complex. Our results indicate that lithium-induced changes at the level of 5HT uptake in platelets are not correlated with concomitant variations in platelet 5HT content and can be dissociated from modifications at the level of imipramine binding sites within the macromolecular complex of the 5HT transporter. Moreover, platelet 5HT uptake is apparently modulated by lithium, with a similar pattern in healthy volunteers and in manic-depressive patients.

Adult↗
PubMed1988

Effects of antidepressants on monoamine transporters.

1. Using [3H]antidepressants, high affinity binding sites associated with the neuronal transporter for serotonin, noradrenaline, dopamine and adrenaline have been identified. 2. The association of high affinity [3H]imipramine binding with the serotonin transporter in brain and platelets is well established. Although the exact relationship between the [3H]imipramine recognition site and the serotonin transporter remains to be elucidated, it appears that the [3H]imipramine labelled component of the serotonin transporter represents a novel receptor that functions to modulate serotonin uptake. 3. Most data available to date support the hypothesis that [3H]imipramine binding to platelet represents a biological marker in depression. The majority of studies indicate that the Bmax of platelet [3H]imipramine binding is lower in depressed, untreated patients than in the control population and that this finding is relatively specific to depression. 4. Among the [3H]antidepressant binding sites associated with the other monoaminergic transporters, the recent identification of [3H]desipramine binding to the neuronal transporter for adrenaline offers novel perspectives. Thus, given the high affinity for [3H]desipramine binding to the adrenaline transporter in the frog heart for not only desipramine but also imipramine and the atypical antidepressants mianserin and iprindol, it is possible that an interaction with the adrenaline transporter is of significance to the clinical effects of antidepressant drugs.

Anti-Anxiety Agents↗
PubMed1987

[3H]desipramine labels with high affinity the neuronal transporter for adrenaline in the frog heart.

Desipramine, a tricyclic antidepressant, inhibits the neuronal uptake of adrenaline and noradrenaline and, as a radioligand, labels the noradrenaline transporter in central and peripheral tissues of the rat. To study whether [3H]desipramine also labels the neuronal adrenaline transporter in vitro, its binding was evaluated in the frog heart, a tissue with a rich adrenergic innervation but virtually devoid of noradrenergic innervation. [3H]Desipramine binding to membranes from the frog heart was of high affinity (Kd = 1.94 nM) and was potently inhibited by nisoxetine and (+)oxaprotiline. Unexpectedly, [3H]desipramine binding to the transporter for adrenaline in the frog heart was also sensitive to inhibition by imipramine and the atypical antidepressants mianserin and iprindol. This is the first study to demonstrate radioligand binding to the neuronal transporter for adrenaline. The results indicate that the pharmacological profile of the transporter for adrenaline may be different from that of the noradrenergic transporter, if species differences can be excluded. It remains to be established if the affinity of imipramine, mianserin and iprindol for the adrenaline transporter contributes to their therapeutic efficacy in depression.

Animals↗
PubMed1987

[3H]-5-methoxytryptoline is not actively accumulated by rabbit platelets.

5-Methoxytryptoline (5-MeO-TLN, 6-methoxytetrahydro-beta-carboline) inhibits with high affinity [3H]-imipramine binding to the serotonin transporter in platelets. To evaluate whether 5-MeO-TLN is a substrate for the serotonin transporter, the accumulation of [3H]-5-MeO-TLN into rabbit platelets was studied in vitro. At short incubation times (5 min), [3H]-5-MeO-TLN accumulation was temperature-sensitive, but not saturable over a concentration range from 0.06 mumol/l to 10 mumol/l. Moreover, [3H]-5-MeO-TLN uptake was not affected by 100 mumol/l ouabain, its structural analogs tryptoline and 5-hydroxytryptoline, nor by the serotonin uptake inhibitors imipramine and citalopram. After longer incubation times (60 min), [3H]-5-MeO-TLN accumulation at 0 degree C approached that seen at 37 degrees C and temperature-sensitive [3H]-5-MeO-TLN uptake could no longer be observed. It is concluded that temperature-sensitive accumulation of [3H]-5-MeO-TLN is not mediated by the serotonin transporter and most likely represents a passive, diffusional process, the rate of which is temperature-dependent. The present studies thus confirm the hypothesis that 5-MeO-TLN affects [3H]-imipramine binding in platelets through a competitive mechanism and not via an allosteric interaction mediated through the substrate recognition site of the macromolecular complex of serotonin transporter.

Animals↗
PubMed1987

Changes in [3H]5-HT uptake and [3H]imipramine binding in platelets after chlorimipramine in healthy volunteers. Comparison with maprotiline and amineptine.

In the platelets of normal healthy volunteers (n = 8) taking chlorimipramine (50 mg/day) for 1 week, the saturable uptake of [3H]5-hydroxytryptamine (5-HT) was fully inhibited at the end of the week, but returned to control values after 2 weeks washout. The Bmax of [3H]imipramine binding was decreased by 63% at the end of the treatment and remained significantly decreased below control values after 1 week washout, whereas the Kd values were increased at the end of the treatment, but had returned to baseline values after 1 week washout. The time course of recovery following the administration of chlorimipramine showed some variation between subjects, but it was necessary to wait up to 4 weeks of washout before the Bmax of [3H]imipramine returned to baseline levels. In contrast, neither 1-week treatment with maprotiline (50 mg/day) nor with amineptine (100 mg/day) changed the parameters of [3H]5-HT uptake or [3H]imipramine binding in platelets from healthy volunteers. These results support the following conclusions. (1) [3H]Imipramine binding in platelets can be down-regulated by relatively low, subtherapeutic doses of chlorimipramine. (2) It is possible to dissociate [3H]imipramine binding parameters from [3H]5-HT uptake because the time course of recovery was clearly different, indicating that [3H]imipramine labels a site linked with, but different from, the 5-HT recognition site in the transporter complex. (3) A washout of antidepressants of 4 weeks may be needed when studying the parameters of [3H]imipramine binding in platelets from depressed patients if the previous medication involved chlorimipramine. For antidepressants like maprotiline or amineptine, that act through mechanisms other than inhibition of 5-HT uptake, the time of washout appears to be less critical, although it is not possible to rule out the existence of some secondary modifications influencing the 5-HT transporter complex.

Adult↗
PubMed1987

Calcium channel receptor binding studies for diltiazem and its major metabolites: functional correlation to inhibition of portal vein myogenic activity.

Pharmacologically distinct but allosterically interacting calcium channel antagonist binding sites have recently been identified using radiolabeled dihydropyridine derivatives (e.g., [3H]nitrendipine) and the benzothiazepine [3H]diltiazem. Whereas the functional significance of the dihydropyridine calcium channel antagonist receptor is well documented, it remains to be established whether drug interactions with the recognition site for [3H]diltiazem within the slow calcium channel or the allosteric interaction of the diltiazem binding site with the dihydropyridine receptor are of physiological significance. In a study of structure-activity relationships, we therefore examined the effects of diltiazem and five of its analogs on the binding of [3H]diltiazem and [3H]nitrendipine to the rat cerebral cortex. In parallel, we studied the effects of these drugs on the spontaneous myogenic contractions of the rat portal vein, a functional test of calcium antagonism. The diltiazem analogs used in this study correspond to its major metabolites in humans, i.e., N-desmethyl-(MA, desacetyl-(M1), N-desmethyl, desacetyl-(M2), O-desmethyl, desacetyl (M4), N-desmethyl, O-desmethyl, desacetyl-diltiazem (M6). Unlabeled diltiazem inhibited [3H]diltiazem binding at 37 degrees C with a pIC50 [-log IC50 (M)] of 6.87. pIC50 values for M1, MA, M2, M4, and M6 were 6.72, 6.49, 6.03, 5.51, and 5.33, respectively. pIC50 values for these drugs on [3H]diltiazem binding were significantly correlated (p less than 0.01) with their pEC50 values for enhancement of [3H]nitrendipine binding to cerebral cortical membranes at 37 degrees C. Maximal enhancement of [3H]nitrendipine binding by diltiazem, M1, MA, M2, M4, and M6 was 73, 50, 9.7, 11, 12, and 52%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Allosteric Regulation↗