Misc Antihistamines Mega Thread

I have been observing BL for a number of year now and have never seen any conclusive threads on antihistamines. So I have decided to try and gather as much knowledge about these substances, with your help, and post it here in the "Antihistamine Mega Thread".

• Please feel free to correct any mistakes in this work.
• Please feel free to add new antihistamines that I have missed, and I will try and update this first post.
• Mods please delete this if there is already a thread with this material.

Molecular Weight

Systemic

Azatadine maleate: 522.56
Brompheniramine maleate: 435.32
Cetirizine hydrochloride: 461.82
Chlorpheniramine maleate: 390.87
Clemastine fumarate: 459.97
Cyproheptadine hydrochloride: 350.89
Desloratadine: 310.8
Dexchlorpheniramine maleate: 390.87
Dimenhydrinate: 469.97
Diphenhydramine hydrochloride: 291.82
Doxylamine succinate: 388.46
Hydroxyzine hydrochloride: 447.83
Hydroxyzine pamoate: 763.29
Loratadine: 382.89
Phenindamine tartrate: 411.45


Indications

Systemic

Rhinitis, perennial and seasonal allergic or vasomotor (prophylaxis and treatment) or Conjunctivitis, allergic (prophylaxis and treatment)

Antihistamines are indicated in the prophylactic and symptomatic treatment of perennial and seasonal allergic rhinitis , vasomotor rhinitis , and allergic conjunctivitis due to inhalant allergens and foods.

Pruritus (treatment) Urticaria (treatment) Angioedema (treatment) Dermatographism (treatment) or Transfusion reactions, urticarial (treatment)
Antihistamines are indicated for the symptomatic treatment of pruritus associated with allergic reactions and of mild, uncomplicated allergic skin manifestations of urticaria and angioedema, in dermatographism, and in urticaria associated with transfusions. Cyproheptadine may be particularly useful for cold urticaria, dermatitis including neurodermatitis and neurodermatitis circumscripta, eczema, eczematoid dermatitis, mild local allergic reactions to insect bites, angioneurotic edema, drug and serum reactions, anogenital pruritus and pruritus of chickenpox. [Antihistamines are also used in the treatment of pruritus associated with pityriasis rosea.]

Sneezing (treatment) or Rhinorrhea (treatment)
Antihistamines are indicated for the relief of sneezing and rhinorrhea associated with the common cold . However, controlled clinical studies have not demonstrated that antihistamines are significantly more effective than placebo in relieving cold symptoms. Non-sedating (i.e., second-generation) antihistamines are unlikely to be useful in the treatment of the common cold symptoms since they do not have clinically significant anticholinergic effects (e.g., drying effects on nasal mucosa).

Anaphylactic or anaphylactoid reactions (treatment adjunct)
Antihistamines are indicated as adjunctive therapy to epinephrine and other standard measures for anaphylactic reactions after the acute manifestations have been controlled, and to ameliorate the allergic reactions to blood or plasma.

Anxiety (treatment) and Tension, psychosis-related (treatment)
Hydroxyzine is indicated for the relief of anxiety and tension associated with psychoneurosis and as an adjunct in organic disease states in which anxiety is manifested. The effectiveness of hydroxyzine as an antianxiety agent for long-term use (for example, more than 4 months) has not been assessed by systematic clinical studies.

Alcohol withdrawal (treatment)
Parenteral hydroxyzine is indicated in the acute or chronic alcoholic with anxiety withdrawal symptoms.

Parkinsonism (treatment) or Extrapyramidal reactions, drug-induced (treatment)
Diphenhydramine is indicated for the symptomatic treatment of parkinsonism and drug-induced extrapyramidal reactions in elderly patients unable to tolerate more potent antidyskinetic medications, for mild cases of parkinsonism in other age groups and, in combination with centrally acting anticholinergic agents, for other cases of parkinsonism.

Diphenhydramine hydrochloride syrup is currently indicated as a non-narcotic cough suppressant for control of cough due to colds or allergy.

Motion sickness (prophylaxis and treatment) or Vertigo (treatment)
Dimenhydrinate and diphenhydramine are indicated for the prevention and treatment of the nausea, vomiting, dizziness, or vertigo of motion sickness.

Nausea or vomiting (prophylaxis and treatment)
Parenteral hydroxyzine is indicated for the control of nausea and vomiting, excluding nausea and vomiting of pregnancy.

Sedation
Diphenhydramine and hydroxyzine are indicated for their sedative and hypnotic effects and as preoperative medications.

Insomnia (treatment)
Diphenhydramine and doxylamine are indicated as nighttime sleep aids to help reduce the time to fall asleep in patients having difficulty falling asleep.

Analgesia adjunct, during surgery Anesthesia, general, adjunct or Anesthesia, local, adjunct
Parenteral hydroxyzine is useful as pre- and postoperative, and pre- and postpartum adjunctive medication to allow reduction in narcotic dosage, and to control anxiety and emesis.

Appetite, lack of (treatment)
Cyproheptadine is used as an appetite stimulant, in adults and children.

Headache, vascular (treatment)
Cyproheptadine is used for treatment of vascular headaches, such as migraine and histamine cephalalgia.

Asthma, bronchial (treatment adjunct)
Cetirizine, and loratadine are used as adjunctive treatment to asthma medications to reduce symptoms and improve bronchodilation in patients with mild atopic asthma.


Contraindications

Systemic

The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (= major clinical significance).

Except under special circumstances, this medication should not be used when the following medical problems exist Hepatic function impairment (desloratadine dosage adjustment recommended due to increases in bioavailability, half-life, and area under the curve. )

Renal function impairment (Desloratadine dosage adjustment is recommended due to increases in plasma concentration and area under the curve )

Risk-benefit should be considered when the following medical problems exist Bladder neck obstruction or Prostatic hypertrophy, symptomatic or Urinary retention, predisposition to

(anticholinergic effects may precipitate or aggravate urinary retention )

Glaucoma, angle-closure, or predisposition to (anticholinergic mydriatic effect resulting in increased intraocular pressure may precipitate an attack of angle-closure glaucoma)

Glaucoma, open-angle (anticholinergic mydriatic effect may cause a slight increase in intraocular pressure; glaucoma therapy may need to be adjusted)

Hypersensitivity to the antihistamine used Caution is recommended when dimenhydrinate, diphenhydramine, or hydroxyzine is used, since their antiemetic action may impede diagnosis of such conditions as appendicitis and obscure signs of toxicity from overdosage of other drugs. For cyproheptadine Peptic ulcer, stenosing Pyloroduodenal obstruction
(anticholinergic effects of cyproheptadine may exacerbate these conditions )

For desloratadine Metabolism of desloratadine, impaired (slow metabolizers of desloratadine may be more susceptible to dose-related adverse events )

Other medical problems, especially angle closure glaucoma, bladder neck obstruction, hepatic or renal impairment (with desloratadine), prostatic hypertrophy, pyloroduodenal obstruction (with cyproheptadine), stenosing peptic ulcer (with cyproheptadine) or urinary retention.


Mechanisms Of Action

Systemic

Antihistaminic (H 1 -receptor)—Antihistamines used in the treatment of allergy act by competing with histamine for H 1 -receptor sites on effector cells. They thereby prevent, but do not reverse, responses mediated by histamine alone. Antihistamines antagonize, in varying degrees, most of the pharmacological effects of histamine, including urticaria and pruritus. Also, the anticholinergic actions of most antihistamines provide a drying effect on the nasal mucosa.

Antianxiety agent—Hydroxyzine's sedative action may be due to a suppression of activity in certain key regions of the subcortical area of the central nervous system (CNS). It is not a cortical depressant.

Antidyskinetic—The actions of diphenhydramine in parkinsonism and in drug-induced dyskinesias appear to be related to a central inhibition of the actions of acetylcholine, which are mediated via muscarinic receptors (anticholinergic action), and to its sedative effects.

Antiemetic; antivertigo agent—The mechanism by which some antihistamines exert their antiemetic, anti–motion sickness, and antivertigo effects is not precisely known but may be related to their central anticholinergic actions. They diminish vestibular stimulation and depress labyrinthine function. An action on the medullary chemoreceptive trigger zone may also be involved in the antiemetic effect.

Antitussive—Diphenhydramine suppresses the cough reflex by a direct effect on the cough center in the medulla of the brain.

Sedative-hypnotic—Most antihistamines cross the blood-brain barrier and produce sedation due to inhibition of histamine N -methyltransferase and blockage of central histaminergic receptors. Antagonism of other central nervous system receptor sites, such as those for serotonin, acetylcholine, and alpha-adrenergic stimulation, may also be involved. Central depression is not significant with cetirizine (low doses), desloratadine, or loratadine because they do not readily cross the blood-brain barrier. Also, they bind preferentially to peripheral H 1 -receptors rather than to central nervous system H 1 -receptors.

Appetite stimulant—Cyproheptadine competes with serotonin for receptor sites, thus blocking the responses to serotonin in vascular, intestinal, and other smooth muscles. It is possible that by altering serotonin activity in the appetite center of the hypothalamus, cyproheptadine stimulates appetite.

Vascular headache suppressant—Cyproheptadine's vascular headache suppressant effect is probably due to its antiserotonin action.

Antiasthmatic— Cetirizine, and loratadine have been shown to cause mild bronchodilation and also to block histamine-induced bronchoconstriction in asthmatic patients. Also, loratadine, have been shown to diminish exercise-induced bronchospasm and hyperventilation-induced bronchospasm. Cetirizine has not been shown to be uniformly effective in preventing allergen- or exercise-induced bronchoconstriction; however, due to its inhibition of late-phase eosinophil recruitment after local allergen challenge, it has been shown to be more effective, in higher doses, than other antihistamines in reducing the symptoms of pollen-induced asthma.


Absorption Data

Systemic

Well absorbed after oral administration.

Note:

Ingestion of food may enhance the absorption of loratadine by 40% and of its active metabolite by 15% .

Food may delay the rate, but not the extent of cetirizine absorption.

In one study involving patients 66 to 78 years of age the extent of absorption and peak plasma levels of loratadine and its metabolite were significantly higher (55%) than those in studies with younger patients.

Desloratadine's absorption is not affected by food. Renal impairment and hepatic impairment requires dosage adjustments due to increased AUC (area under the concentration time curve).


Protein Binding Data

Systemic


Cetirizine—93%.
Chlorpheniramine—72%.
Desloratadine—82 to 87%. 3-hydroxydesloratadine (active metabolite): 85 to 89%
Diphenhydramine—98 to 99%.
Loratadine—97% (at concentrations of 2.5 to 100 ng/mL). Descarboethoxyloratadine (active metabolite): 73 to 77% (at concentrations of 0.5 to 100 ng/mL).


Biotransformation Data

Systemic

Hepatic (cytochrome P-450 system); some renal. Of the second-generation antihistamine , loratadine is metabolized by the hepatic cytochrome P-450 system and have active metabolites ; however, cetirizine is minimally metabolized and excreted unchanged primarily through the kidneys.

Desloratadine is extensively metabolized to 3-hydroxydesloratadine, an active metabolite, which is subsequently glucuronidated. The enzymes responsible for the metabolism have not been identified .


Half Life

Systemic

Elimination

Azatadine—12 hours.
Brompheniramine—25 hours.

Cetirizine—8 hours (range, 6.5 to 10 hours).
In dialysis patients: 20 hours.
In children: 4.1 to 6 hours.

Chlorpheniramine—14 to 25 hours.
Desloratadine—27 hours.
Diphenhydramine—1 to 4 hours.
Hydroxyzine—20 to 25 hours.
Loratadine—3 to 20 hours (mean, 8.4 hours). Descarboethoxyloratadine (active metabolite): 8.8 to 92 hours (mean, 28 hours).

Note:
In children, cetirizine, chlorpheniramine, and hydroxyzine have been found to have shorter elimination half-life values.


Elimination Data

Systemic

Most of the antihistamines studied (except cetirizine) are excreted as metabolites within 24 hours.

Cetirizine
Approximately 60% of the total dose administered is excreted unchanged in urine within 24 hours; about 10% is excreted in feces.

Desloratadine
Approximately 87% of a 14 C-desloratadine dose was equally recovered in urine and feces.

Loratadine
Approximately 80% of the total dose administered is excreted equally in urine and feces in the form of metabolic products within 10 days. Twenty-seven percent of the total dose is excreted in the urine in the conjugated form within 24 hours.


Adverse Effects

Systemic

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent or rare Anaphylaxis (cough difficulty swallowing dizziness fast heartbeat hives itching puffiness or swelling of the eyelids or around the eyes, face, lips or tongue shortness of breath skin rash tightness in chest unusual tiredness or weakness wheezing) blood dyscrasias sore throat) fever) unusual bleeding or bruising) unusual tiredness or weakness) — with azatadine, brompheniramine, cyproheptadine, and dexchlorpheniramine cardiac arrhythmias/palpitations/tachycardia fast pounding or irregular heartbeat or pulse) — less frequent or rare with azatadine, cetirizine, clemastine, cyproheptadine, desloratadine, dexchlorpheniramine, diphenhydramine, or loratadine cholestasis, hepatitis or other hepatic function abnormalities (abdominal or stomach pain chills clay-colored stools or dark urine diarrhea dizziness fever headache itching) convulsions or seizures edema (swelling ) paresthesia or neuritis (burning prickly sensations tingling) —with cyproheptadine urticaria (hives or welts; itching; redness of skin; skin rash) —with desloratadine


Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent Drowsiness dryness of mouth, nose, or throat gastrointestinal upset, stomach pain, or nausea —with azatadine and diphenhydramine headache —with desloratadine increased appetite or weight gain —with , cyproheptadine pharyngitis (body aches or pain congestion cough dryness or soreness of throat fever hoarseness runny nose tender, swollen glands in neck trouble in swallowing voice changes) — with desloratadine. thickening of mucus —with azatadine and cyproheptadine

Note:
Tolerance to central nervous system effects may develop quickly with some antihistamines, so that sedation is no longer troublesome after a few days.

Incidence of sedation may increase when the recommended doses of loratadine are exceeded.

Incidence less frequent or rare
Blurred vision or any change in vision —with azatadine, cetirizine, cyproheptadine, diphenhydramine, and loratadine, confusion —with azatadine, cetirizine, cyproheptadine, diphenhydramine, and loratadine, ; not reported with diphenhydramine difficult or painful urination —with azatadine, cetirizine, chlorpheniramine, cyproheptadine, dexclorpheniramine, and loratadine dizziness —except with brompheniramine and hydroxyzine drowsiness —with brompheniramine, chlorpheniramine; reported with high doses of desloratadine and loratadine dryness of mouth, nose, or throat —with cetirizine and loratadine dysmenorrhea ( difficult or painful menstruation) — with desloratadine dyspepsia ( acid or sour stomach; belching; heartburn; indigestion; stomach discomfort upset or pain) —with desloratadine increased appetite or weight gain —with cetirizine and loratadine increased sweating —with azatadine, cetirizine, chlorpheniramine, cyproheptadine, loratadine, and fatigue ( unusual tiredness or weakness) — with desloratadine loss of appetite —with cetirizine, chlorpheniramine, cyproheptadine, and loratadine myalgia ( joint pain; swollen joints; muscle aching or cramping; muscle pains or stiffness; difficulty in moving) — with desloratadine nausea — with desloratadine paradoxical reaction (nightmares unusual excitement, nervousness, restlessness, or irritability) —except with azatadine, chlorpheniramine, cyproheptadine, desloratadine, hydroxyzine, and loratadine photosensitivity (increased sensitivity of skin to sun) —with azatadine, cetirizine, cyproheptadine, and loratadine, ringing or buzzing in ears —with azatadine, cetirizine, cyproheptadine, and loratadine skin rash — with azatadine, brompheniramine, cetirizine, clemastine, cyproheptadine, and loratadine gastrointestinal upset, stomach pain, or nausea —with cetirizine, clemastine, cyproheptadine, and loratadine tachycardia (fast heartbeat) —with azatadine, cetirizine, cyproheptadine, and loratadine, thickening of mucus — with cyproheptadine, dexchlorpheniramine and diphenhydramine abnormal coordination (clumsiness or unsteadiness) constipation diarrhea early menses fatigue tremor vomiting —with cyproheptadine

Note:
Confusion; difficult or painful urination; drowsiness; dizziness; and dryness of mouth, nose, or throat are more likely to occur in the elderly.

Nightmares, unusual excitement, nervousness, restlessness, or irritability is more likely to occur in children and elderly patients.

Anticholinergic effects (clumsiness or unsteadiness severe drowsiness severe dryness of mouth, nose, or throat flushing or redness of face shortness of breath or troubled breathing) — especially with azatadine and clemastine cardiac arrhythmias (fast or irregular heartbeat) — ; less frequent with azatadine and clemastine CNS depression (severe drowsiness) CNS stimulation (hallucinations, seizures, trouble in sleeping) hypotension (feeling faint)

Note:
Anticholinergic and CNS stimulant effects are more likely to occur in children with overdose. Hypotension may also occur in the elderly at usual doses.

Anticholinergic and CNS effects may be less likely to occur with , cetirizine, desloratadine or, loratadine, than with the first-generation antihistamines.

somnolence (sleepiness or unusual drowsiness) —especially with desloratadine


Interactions

Systemic

The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (= major clinical significance):

Note:
It is not likely that cetirizine, desloratadine, or loratadine will interact with most of the following medications because they lack significant anticholinergic and CNS actions. However, cetirizine and loratadine have been shown to cause dose-related CNS effects (e.g., sedation); and cetirizine has minimal anticholinergic effects.

Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Antacids, magnesium or aluminum containing
(administration of fexofenadine within 15 minutes of an aluminum or magnesium containing antacid decreased fexofenadine AUC by 41% and C max by 43%. )

Alcohol or CNS depression–producing medications, other
(concurrent use may potentiate the CNS depressant effects of either these medications or antihistamines; also, concurrent use of maprotiline or tricyclic antidepressants may potentiate the anticholinergic effects of either antihistamines or these medications)

Anticholinergics or other medications with anticholinergic activity
(anticholinergic effects may be potentiated when these medications are used concurrently with antihistamines; patients should be advised to report occurrence of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy)

Apomorphine
(prior administration of dimenhydrinate, diphenhydramine, doxylamine, or hydroxyzine may decrease the emetic response to apomorphine in the treatment of poisoning)

Potent inhibitors of the cytochrome P450 enzyme system such as: Erythromycin Fluconazole Itraconazole Ketoconazole Metronidazole Miconazole
(concurrent use of these medications may increase plasma levels of loratadine; there are no reports to date of serious ventricular arrhythmias associated with increased plasma levels of loratadine)

(concurrent use of fexofenadine with co-administered ketoconazole and erythromycin may lead to increased plasma levels of fexofenadine, and may also enhance fexofenadine gastrointestinal absorption and decrease fexofenadine gastrointestinal excretion )

Monoamine oxidase (MAO) inhibitors, including furazolidone and procarbazine
(concurrent use of MAO inhibitors with antihistamines may prolong and intensify the anticholinergic and CNS depressant effects of antihistamines; concurrent use is not recommended)

Ototoxic medications
(concurrent use with antihistamines may mask the symptoms of ototoxicity such as tinnitus, dizziness, or vertigo)

Photosensitizing medications
(concurrent use of these medications with antihistamines may cause additive photosensitizing effects)

Other medications, especially alcohol or other CNS depressants, anticholinergics or other medications with anticholinergic activity, or MAO inhibitors

Very nice thread Nabollocks, I'll add this to the Mega Threads Sticky for you.

An obvious omission to the list is promethazine.

bigger than shit

in addition to promethazine, cyclazine is another common anti histamine that doesn't appear on the list.

Can you all help by trying to gather the information on these other antihistamines. Using the headings in the original post should be a good guide for topics.

And yes, it is bigger than shit, but hopefully we can have all the info we need in one spot.

Here are the headings to research if you cant be bothered reading the mother post again...

Molecular Weight
Indications
Contraindications
Mechanisms Of Action
Absorption Data
Protein Binding Data
Biotransformation Data
Half Life
Elimination Data
Adverse Effects
Interactions

And it would be great if we could include references. I will try and keep a list of references at the end of the post.

Obviously it does not matter if you cannot find all the relevant information, but the more the better.

When I have a spare moment I will try to update this information.

We need to define all the common Tricyclic Antidepressants as well, as these are every bit as much an antihistamine as they are an antidepressant. These include:

amitriptyline
amoxapine
doxepin
imipramine
trimipramine

Do we want to include the tetracyclic antidepressants as well? This class of antihistamines would include drugs such as:

Mirtazapine
Mianserin

Do you guys think I should include these antihistamines:

antergan
piperoxan
thymoxyethyldiethylamine
promethazine
mepyramine
tripelenamine
astemizole
terfenadine
temelastine
epinastine
acrivastine
mequitazine

Or do you think it is worth trying to keep to the more commonly used antihistamines?

Cyclizine*

so out of that amazing list of antihistamines which one would be the best for getting rid of that pesky opiate itch. I have tried loratadine and im not sure how well it actually works. and i hear about Diphenhydramine being the go to antihistamine for this.

^ IMO, starting with the best (and relatively common), we have: promethazine, diphenhydramine, hydroxyzine, doxylamine.

Only diphenhydramine and doxylamine are OTC in the USA.

Some info on promethazine would be good, the list seems to be mainly the ethanolamine anthistamines....promethazine is quite different??

Does anyone know how hydroxyzine compares to other anti-histamines?
Normally I get restless when I take diphenhydramine and doxylamine, but do eventually fall asleep.
Is hydroxyzine any better with regard to that side affect?

Promethazine is an antipsychotic as well as being an antihistamine.

Artificial Emotion said:

Promethazine is an antipsychotic as well as being an antihistamine.

Click to expand...

Yeah,
...and?8)

Do you have any info about that subject pertaining to promethazine that you want to post or want someone (possibly me) to find for you? Maybe we should add a section about that in the initial post for the Mega Thread?

I just don't understand the point of the comment, are you just trying to tell people? If so, I could definitely expand on this subject if there is demand for it.

Just try to help

-TheMatador

TheMatador said:

I just don't understand the point of the comment, are you just trying to tell people?

-TheMatador

Click to expand...

Yes.

I thought it was an interesting fact that people would be interested in knowing.

Just like the typical antipsychotic chlorpromazine, promethazine is a phenothiazine derivative but the antipsychotic strength of the drug is low meaning that it will not significantly block the dopaminergic action of recreational drugs.

Is that better?

^interesting insight/input/knowledge..thanks for the contribution (FYI, don't fuck around with Zyprexa.)

Cyclizine, Promethazine, Hydroxyzine, Diphenhydramine are probably the most important anti-Histamines for recreational IV pill users.

Taken orally (though not for a deleriant effect), the rest of the OTC and RX anti-Histamines can basically be rated by: strength of anti-histaminic action and amount of sedation. Meclizine, Loratidine and Ceterizine are, for most people, non-invasive. They don't drastically effect recreational/addictive drugs' method of action or duration, they don't produce any or for most very little sedation- when taken orally. Clemastine, Doxylamine, Diphenhydramine, etc produce better anti-histaminic activity in some but produce much more sedation and do meddle in the safety and efficacy of the high of recreational/addictive drugs. Aside from the first 4 mentioned, I doubt any other commonly prescribed or OTC anti-Histamine produces a rush or pleasurable aspect to another drug via IV.

Phenyltoloxamine can produce euphoria from being taken orally in therapeutic doses. I have experienced this a few times, a mood lift 30-90 minutes after consuming two or three OTC tablets. Mild sedation. Ethanolamine AH's can produce euphoria in some people in certain situations when taken orally. I've tried in vain to re-create this effect, while other times it happens when my primary goal was to use it as a sleep aid or pain reliever adjutant.

Perhaps this is the wrong place for this post but here goes.
How safe/dangerous are anti-histamines compared to other drugs (specifically loratadine)
Would daily use of the drug for hayfever carry risks? what are these risks? (More/Less risky than daily Cannabis use?)
Can it cause addiction or withdrawel effects in individuals?
My parents seem to be forcing me to take loratadine daily and im slightly skeptical about it.
Im fine just putting up with hayfever, its not that bad and i actually enjoy sneezing a lot
Funny how smoking weed is out of the question but forcing loratadine into my system daily is ok from their perspective. Ignorance FTW!

The drug orphenadrine, which is closely related to diphenhydramine is primarily used as an anticholinergic drug. It is effective in helping opiates 'find the pain'. It can also be used as an antihistamine for hayfever sufferers or for controlling the side effects of opioids. The great thing about this drug is that even on its own it can product mild feelings of euphoria:

Euphoria is an effect reported by many patients and orphenadrine has been investigated for use against depression, as first reported in June 1958 in the American Journal of Psychiatry.

Click to expand...

See:

ROBITSCHER JB, PULVER SE (June 1958 ). "Orphenadrine in the treatment of depression; a preliminary study". The American journal of psychiatry 114 (12): 1113–5. PMID 13533653. http://ajp.psychiatryonline.org/cgi/pmidlookup?view=long&pmid=13533653.

In my experience it has proven to be the best antihistamine potentiators on the market and I would recommend it to anyone.