Histamine H1 receptors are antagonistic to mepyraminemaleate. For H1, H2, and H3 receptors, the Kd values are 0.8 nM, 5200 nM, and >3000 nM, in that order [1]. The H1 receptor has a pKd of 9.4 [2]. In the brains of guinea pigs (0.8 nM), rats (9.1 nM), DDT1-MF-2 and BC3H1 cells (276 nM), and rat brains, mepyramine binds to H1 receptors with distinct Kd [1]. Mepyramine lowers the maximal response to ATP in CHO-gpH1 cells and lowers InsP levels in CHO-gpH1 cells with a log EC50 of -7.94 ± 0.11 [3].

Intraperitoneal injections of mepyramine at doses of 10 and 20 mg/kg considerably suppressed the second-stage nociceptive response in rats, but injections at a value of 5 mg/kg had no discernible effect [4].

Absorption, Distribution and Excretion
H1 receptor antagonists are readily absorbed from the gastrointestinal tract. Peak plasma concentrations are reached within 2 to 3 hours after oral administration, and the effect typically lasts 4 to 6 hours; however, some drugs have a longer duration of action… /Histamine Antagonists: H1 Receptor Antagonists/ Children clear H1 receptor antagonists faster than adults, while clearance is slower in patients with severe liver disease. /Histamine Antagonists: H1 Receptor Antagonists/

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Metabolism/Metabolites The primary site of metabolic transformation is the liver. /Antichrists/ H1 receptor blockers are among many drugs that induce hepatic microsomal enzymes, which may promote their own metabolism. /Histamine Antagonists: H1 Receptor Antagonists/

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Occasional use of low doses of piracetam during lactation may be acceptable. Higher doses or prolonged use may affect the infant or reduce milk production, especially when used in combination with sympathomimetic drugs (such as pseudoephedrine) or before lactation is fully established. Non-sedating antihistamines are a better alternative.
◉ Effects on Breastfed Infants
As of the revision date, no published information was found regarding piracetam. In a telephone follow-up study, mothers reported that 10% of their infants experienced irritability and colic after taking various antihistamines, and 1.6% experienced lethargy. All adverse reactions were non-medical, and all infants were not exposed to piracetam.
◉ Effects on Lactation and Breast Milk
Higher doses of injected antihistamines can lower baseline serum prolactin levels in non-lactating women and early postpartum women. However, pre-administration of antihistamines by postpartum mothers does not affect suckling-induced prolactin secretion. Whether lower oral doses of antihistamines have the same effect on serum prolactin, and whether their effect on prolactin has any impact on breastfeeding success, is currently unstudied. Prolactin levels in established lactating mothers may not affect their breastfeeding ability.

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Interactions
Concomitant use of ototoxic drugs and antihistamines may mask ototoxic symptoms such as tinnitus, dizziness, or vertigo. /Antihistamines/
Concomitant use of monoamine oxidase (MAO) inhibitors with antihistamines may prolong and enhance the anticholinergic and central nervous system depressant effects of antihistamines; concomitant use is not recommended. /Antihistamines/
Concomitant use with alcohol or other central nervous system depressants may enhance the central nervous system depressant effects of these drugs or antihistamines; furthermore, concomitant use with maprotiline or tricyclic antidepressants may enhance the antihistamine or anticholinergic effects of these drugs. /Antihistamines/
When anticholinergic drugs or other drugs with anticholinergic activity are used in combination with antihistamines, the anticholinergic effect may be enhanced; patients should be advised to report gastrointestinal problems promptly, as combined use may lead to paralytic ileus. Antihistamines
Concurrent use of other photosensitizing drugs and antihistamines may produce additive photosensitizing effects.

[1]. Hill SJ. Distribution, properties, and functional characteristics of three classes of histamine receptor. Pharmacol Rev. 1990 Mar;42(1):45-83.

[2]. Selective ligands as tools to study histamine receptors. Eur J Med Chem. 2000 Jan;35(1):5-20.

[3]. Mepyramine, a histamine H1 receptor inverse agonist, binds preferentially to a G protein-coupled form of the receptor and sequesters G protein. J Biol Chem. 2004 Aug 13;279(33):34431-9.

[4]. Effects of mepyramine and famotidine on the physostigmine-induced antinociception in the formalin test in rats. Pak J Biol Sci. 2008 Nov 15;11(22):2573-8.

Pyrilamine is a viscous, brown liquid. (NTP, 1992)
Pyrilamine is an ethylenediamine derivative with the structure of an ethylenediamine molecule, in which one amino nitrogen atom is replaced by two methyl groups, and the other amino nitrogen atom is replaced by a 4-methoxybenzyl and a pyridin-2-yl group. It is an H1 receptor antagonist. It is an ethylenediamine derivative and also an aromatic ether.
Pyrilamine (or pyramine) targets the H1 receptor. It is a first-generation antihistamine. However, it can rapidly penetrate the brain, thus often causing side effects such as drowsiness. It was once added to over-the-counter combination preparations for treating cold and menstrual symptoms, but is currently considered an unapproved prescription drug for treating coughs, colds, or allergies.
Histamine H1 receptor antagonist. It has mild hypnotic effects and some local anesthetic effects, and can be used to treat allergies (including rashes), both parenterally and topically. It is a common ingredient in cold medicines.
See also: Pyrilamine maleate (in salt form). Drug Indications This drug is indicated for the treatment of allergic diseases, relief of allergic reaction symptoms, and treatment of pruritic skin conditions. Mechanism of Action Mepiracetam is a histamine H1 receptor inverse agonist. It binds to the G protein-coupled form of the receptor, promoting the H1 receptor to enter a G protein-coupled inactive state, thereby interfering with Gq/11-mediated signaling. Mepiracetam competes with histamine for H1 receptor sites on the surface of effector cells, thereby inhibiting histamine-induced subcutaneous edema, erythema, and pruritus. The sedative effect of mepiracetam occurs at the subcortical level of the central nervous system. Antihistamines used to treat allergies act by competing with histamine for H1 receptor sites on effector cells. They can prevent (but cannot reverse) reactions mediated solely by histamine. Antihistamines antagonize most of the pharmacological effects of histamine to varying degrees, including urticaria and pruritus. In addition, the anticholinergic effects of most antihistamines can cause nasal dryness. H1 receptor antagonists inhibit most smooth muscle responses to histamine. The antagonistic effect of histamine on the contraction of respiratory smooth muscle is readily demonstrated both in vivo and in vitro. /Histamine antagonists: H1 receptor antagonists/
H1 receptor antagonists potently block the effects of histamine, thereby reducing increased vascular permeability and the formation of edema and wheals. /Histamine antagonists: H1 receptor antagonists/
Some H1 receptor antagonists have local anesthetic activity… /Histamine antagonists: H1 receptor antagonists/
For more complete data on the mechanisms of action of piracetam (6 in total), please visit the HSDB record page.

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Therapeutic Uses
Antihistamines; Histamine H1 Receptor Antagonists
Antihistamines are indicated for the prevention and treatment of perennial and seasonal allergic rhinitis, vasomotor rhinitis, and allergic conjunctivitis caused by inhaled allergens and foods. /Antihistamines; already included on the US product label/
Antihistamines are indicated for the treatment of itching associated with allergic reactions, and mild, uncomplicated allergic skin manifestations such as urticaria and angioedema, dermatographia, and transfusion-associated urticaria. /Antihistamines; already included on the US product label/
Antihistamines are also used to treat itching associated with pityriasis rosea. /Antihistamines; this information is not included on the US product label/
For more complete data on the therapeutic uses of piracetam (11 in total), please visit the HSDB record page.

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Drug Warnings
Use is not recommended for newborns or premature infants because this age group is more sensitive to anticholinergic side effects (such as central nervous system excitation) and is more prone to seizures. Children taking antihistamines may experience paradoxical reactions characterized by hyperexcitability. /Antihistamines/
Elderly patients are more likely to experience dizziness, sedation, confusion, and hypotension after taking antihistamines. Elderly patients are particularly susceptible to the anticholinergic side effects of antihistamines, such as dry mouth and urinary retention (especially in men). If these side effects occur and persist or are severe, discontinuation of the medication should be considered. /Anthistamines/
Prolonged use of antihistamines…may reduce or suppress saliva production, leading to tooth decay, periodontitis, oral candidiasis, and discomfort. /Anthistamines/
H1 receptor antagonists are best suited for acute exudative allergies presenting with symptoms of rhinitis, urticaria, and conjunctivitis. However, their effect is limited to symptom relief, limited to suppressing the symptoms caused by the histamine-antibody reaction. These medications do not reduce the intensity of this reaction, which is the cause of various allergic diseases. /Histamine Antagonists: H1 Receptor Antagonists/
For more complete data on drug warnings for piracetam (11 in total), please visit the HSDB record page.

C21H27N3O5

401.4562

401.195

59-33-6

59-33-6;91-84-9;6036-95-9 (HCl);

4992

White to off-white solid powder

423.8ºC at 760 mmHg

100-101ºC

210.1ºC

2.37

0

4

7

21

277

0

YECBIJXISLIIDS-UHFFFAOYSA-N

InChI=1S/C17H23N3O/c1-19(2)12-13-20(17-6-4-5-11-18-17)14-15-7-9-16(21-3)10-8-15/h4-11H,12-14H2,1-3H3

N'-[(4-methoxyphenyl)methyl]-N,N-dimethyl-N'-pyridin-2-ylethane-1,2-diamine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~249.09 mM)
H2O : ~50 mg/mL (~124.55 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.23 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.23 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (249.09 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)