Drugs online research references
Br J Pharmacol. 1992 Aug;106(4):900-5.
Blockade of Na+ current by promethazine in guinea-pig ventricular myocytes.
Tanaka H, Habuchi Y, Nishimura M, Sato N, Watanabe Y.
Department of Laboratory Medicine, Kyoto Prefectural University of Medicine, Japan.
1. To elucidate the antiarrhythmic mechanism of promethazine, its effects on the fast Na+ current (INa) were examined in single guinea-pig ventricular myocytes by whole-cell voltage clamp methods. 2. Promethazine blocked INa with a KD of 42.6 microM and Hill's coefficient of 1.1 at a holding potential of -140 mV. 3. The INa blockade was enhanced at a less negative holding potential of -80 mV with a change of KD to 4.4 microM. Although 10 microM promethazine did not change the inactivation time constants of INa, it shifted the steady-state inactivation curve (h infinity curve) toward more negative potentials by 19.5 mV with the slope factor unaffected. 4. Double pulse experiments revealed that the development of blockade followed two-exponential functions having time constants of 7 and 220 ms at -20 mV. 5. Promethazine slowed the repriming of INa. This was associated with the development of slow phase having a time constant of 1160 +/- 59 ms. 6. Promethazine produced a profound use-dependent block when the cell was repeatedly stimulated with interpulse intervals shorter than 1 s. However, short pulses of 2 ms duration hardly produced such a use-dependent block. Hence, open channel blockade is considered to play a minor role in the promethazine action on INa. 7. These results suggest that promethazine blocks cardiac INa in a manner similar to class I antiarrhythmic drugs and that this effect may account for its antiarrhythmic action.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1327391&dopt=Abstract
J Pharmacol Exp Ther. 1988 Apr;245(1):311-8.
Increment of calmodulin in proportion to enhancement of non-nicotinic responses after preganglionic stimulation of the dog cardiac sympathetic ganglia.
Kushiku K, Araki Y, Furukawa T, Iwasa T, Inoue N, Miyamoto E.
Department of Pharmacology, School of Medicine, Fukuoka University, Japan.
The possible involvement of calmodulin in ganglionic function was investigated. Drugs were given directly into the cardiac sympathetic ganglia through the right subclavian artery (i.a.), unless otherwise stated. Positive chronotropic responses to angiotensin II (0.1 and 0.2 micrograms) were enhanced after repetitive high frequency preganglionic stimulation to the right stellate ganglion. After the stimulation, positive chronotropic responses to bethanechol (2.5, 5 and 10 micrograms), but not those to dimethylphenylpiperazinium (2.5, 5 and 10 micrograms), also were enhanced. The enhancement of response to angiotensin II was not affected by i.v. pretreatment with hexamethonium (40 mg/kg) plus atropine (1 mg/kg) or nifedipine (1 mg/kg). Responses to angiotensin II were not enhanced by A23187 (0.3 mg). The enhanced response to angiotensin II after the stimulation was reduced by the calmodulin antagonists, trifluoperazine (0.1, 0.2 and 0.4 mg) and by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (0.5, 1 and 2 mg), but not by promethazine (1 mg) and N-(6-aminohexyl)-1-naphthalenesulfonamide (0.5, 1 and 2 mg). The enhanced response to bethanechol after the stimulation also was inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide. Pretreatment with N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide before the stimulation prevented development of the enhancement in responses to the peptide. The inhibition of endogenous protein synthesis by cycloheximide, 2.5 or 5 mg/kg i.v. 6 hr before surgical procedures, strongly inhibited development of the enhancement in responses to angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2896238&dopt=Abstract
Neuropsychobiology. 1984;12(2-3):134-7.
Diazepam, promethazine and propiomazine as hypnotics in elderly inpatients.
Viukari M, Miettinen P.
Diazepam 5 mg, promethazine 25 mg, propiomazine 25 mg, and placebo as sleeping aids were studied in 40 elderly inpatients. The drugs were administered in a random order, double-blind, on 21 nights. All active drugs were found effective in the mentally normal elderly, but in the psychogeriatric group of 20 patients, only propiomazine very significantly reduced the number of nocturnal awakenings and only diazepam almost significantly shortened the initial sleep latency, although duration of sleep was prolonged in both groups. There was neither loss of efficacy of the trial drugs nor rebound on withdrawal. Psychomotor skills and serum prolactin levels remained unaffected.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6152029&dopt=Abstract
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